Anal Fissure
An anal fissure is a small tear or cut in the lining of the anus, specifically in the anoderm, the sensitive tissue of the anal canal. This common condition is often characterized by significant pain, especially during and after bowel movements, and may be accompanied by bright red rectal bleeding[1].
The biological basis of an anal fissure typically involves trauma to the anal lining, most commonly from passing hard, large, or dry stools, or from chronic constipation or prolonged diarrhea[2]. Once a tear occurs, the pain can trigger a reflex spasm of the internal anal sphincter muscle. This spasm reduces blood flow to the injured area, which impedes healing and can lead to a vicious cycle of pain, sphincter spasm, and non-healing, often resulting in a chronic fissure. While primarily mechanical, individual variations in tissue elasticity, sphincter tone, and inflammatory response, potentially influenced by genetic factors, might predispose some individuals to developing or experiencing slower healing of anal fissures[3].
Clinically, anal fissures are diagnosed based on symptoms and physical examination. They are a significant cause of discomfort and can severely impact an individual’s quality of life. Treatment often begins with conservative measures, including dietary modifications to soften stools, fiber supplements, stool softeners, sitz baths, and topical medications that help relax the internal anal sphincter [1]. For chronic fissures that do not respond to conservative management, surgical options, such as lateral internal sphincterotomy, may be considered to reduce sphincter spasm and promote healing.
Beyond the physical symptoms, anal fissures carry considerable social importance. The intense pain and fear of defecation can lead to avoidance behaviors, exacerbating constipation and prolonging the condition. This can result in psychological distress, including anxiety and embarrassment, and may affect daily activities and overall well-being. The prevalence of anal fissures across various age groups, from infants to older adults, underscores its broad impact on public health and the need for effective management and awareness.
Limitations
Section titled “Limitations”Genetic studies, particularly those investigating complex traits like anal fissure, are subject to various limitations that can impact the interpretation and generalizability of findings. Acknowledging these constraints is crucial for a balanced understanding of the current research landscape and for guiding future investigations.
Methodological and Statistical Considerations
Section titled “Methodological and Statistical Considerations”Many genetic studies are often constrained by sample sizes that may be insufficient to reliably detect genetic variants with small effect sizes, which are characteristic of complex traits. This limitation can lead to an overestimation of the effect sizes of initially identified variants, a phenomenon known as effect-size inflation, and can contribute to difficulties in replicating findings across independent cohorts. Furthermore, the design of studies and the selection criteria for participants can introduce cohort bias, meaning the characteristics of the studied population may not fully represent the broader population, thereby limiting the generalizability of any identified genetic associations. Addressing these challenges necessitates larger, well-powered studies and rigorous replication efforts to confirm initial discoveries and accurately assess their true genetic impact.
Phenotypic Definition and Population Heterogeneity
Section titled “Phenotypic Definition and Population Heterogeneity”A significant limitation in genetic research often stems from the lack of diversity within study cohorts, which frequently consist predominantly of individuals of European descent. This demographic imbalance poses challenges for generalizing genetic findings to populations of different ancestries, as genetic architectures, allele frequencies, and environmental influences can vary considerably across ethnic groups, potentially rendering results biased or less relevant for underrepresented populations. Moreover, the precise definition and measurement of the anal fissure phenotype itself can vary significantly across different research efforts, ranging from patient self-reports to diverse clinical diagnostic criteria. Such phenotypic heterogeneity can obscure genuine genetic signals or lead to inconsistencies when comparing findings from different studies.
Complex Etiology and Unaccounted Factors
Section titled “Complex Etiology and Unaccounted Factors”The development of complex traits like anal fissure is influenced by an intricate interplay between genetic predispositions and various environmental factors, including lifestyle, diet, and the composition of the gut microbiome. Current genetic studies frequently struggle to comprehensively account for these environmental factors or the nuanced gene-environment interactions, which can act as confounders by masking or modifying the effects of specific genetic variants. The concept of “missing heritability” further highlights the substantial gap between the heritability estimated from family studies and the genetic variation explained by currently identified common variants, suggesting that a significant portion of the genetic architecture remains undiscovered. This unexplained heritability may be attributed to rare variants, epigenetic modifications, or complex gene-gene and gene-environment interactions that are not yet fully captured by existing research methods.
Variants
Section titled “Variants”The SLC35F3 gene, or Solute Carrier Family 35 Member F3, encodes a protein belonging to the extensive family of solute carrier transporters. These proteins are fundamental for facilitating the movement of various substances, including ions, nutrients, and waste products, across cellular membranes, thereby playing crucial roles in cellular metabolism and maintaining cellular homeostasis [4]. While the precise substrates and specific physiological functions of SLC35F3 are still areas of ongoing research, many members of the SLC35 family are recognized for their involvement in nucleotide-sugar transport, processes essential for proper glycosylation[5]. The proper functioning of such transporters is vital for maintaining cellular integrity and enabling cells to respond effectively to various physiological stressors, including inflammatory signals [6].
The genetic variant rs4333882 is a single nucleotide polymorphism (SNP) situated within an intron of theSLC35F3 gene [7]. As an intronic variant, rs4333882 does not directly alter the amino acid sequence of the SLC35F3 protein. However, intronic variants can significantly influence gene expression through several indirect mechanisms[8]. For example, rs4333882 might affect the efficiency or accuracy of mRNA splicing, potentially leading to the production of altered protein isoforms or reduced levels of the fully functional SLC35F3 protein [9]. Alternatively, this variant could be located within or near regulatory elements that modulate the transcription rate of the SLC35F3 gene, thereby impacting the overall cellular availability of the transporter protein [10].
Variations in genes like SLC35F3and their influence on cellular transport mechanisms may contribute to the pathophysiology of conditions such as anal fissure. Anal fissures are frequently characterized by increased internal anal sphincter tone, impaired tissue healing, and localized inflammation[11]. If the rs4333882 variant leads to altered SLC35F3 function, it could potentially affect cellular processes critical for smooth muscle cell function, such as energy metabolism or calcium handling, thereby influencing the hypertonia of the sphincter[12]. Furthermore, dysregulation of solute transport can impact inflammatory pathways or the cellular response to oxidative stress, both of which are known contributors to the chronic nature and poor healing observed in anal fissures [13]. Thus, rs4333882 ’s potential impact on SLC35F3expression or function presents a plausible, albeit indirect, link to the development or persistence of anal fissure by affecting fundamental cellular processes[14].
Key Variants
Section titled “Key Variants”| RS ID | Gene | Related Traits |
|---|---|---|
| rs4333882 | SLC35F3 | diverticular disease anal fissure digestive system disease, abdominal abscess |
Signs and Symptoms
Section titled “Signs and Symptoms”Anal fissures present with a characteristic constellation of symptoms and objective signs that guide diagnosis and management. The clinical presentation often varies based on the acuity of the fissure, individual pain tolerance, and the presence of any underlying conditions.
Primary Symptoms: Pain and Bleeding Characteristics
Section titled “Primary Symptoms: Pain and Bleeding Characteristics”Anal fissures are primarily characterized by intense pain and rectal bleeding, which are often the initial complaints prompting medical evaluation. The pain is typically described as sharp, tearing, or burning, occurring during and immediately after defecation. This discomfort can be severe, persisting for minutes to several hours post-bowel movement, and often leads to a fear of defecation, contributing to a vicious cycle of constipation and further trauma. The severity and duration of pain are subjectively assessed through patient history, often quantified using visual analog scales (VAS) or numerical rating scales (NRS) to track the patient’s experience and response to treatment. Rectal bleeding is another common symptom, typically presenting as small amounts of bright red blood visible on toilet paper, streaking the surface of the stool, or occasionally dripping into the toilet bowl. The presence and characteristics of this bleeding are noted during the clinical interview and confirmed by visual inspection. These primary symptoms, particularly the severe, post-defecation pain and bright red bleeding, are highly indicative of an anal fissure, though a comprehensive evaluation is crucial for differential diagnosis.
Physical Examination Findings and Diagnostic Approaches
Section titled “Physical Examination Findings and Diagnostic Approaches”The definitive diagnosis of an anal fissure relies on the identification of a linear tear or ulcer in the anoderm during physical examination. This tear is most frequently located in the posterior midline (the 6 o’clock position when the patient is in lithotomy position), although anterior midline fissures also occur. Chronic fissures may exhibit additional objective signs, such as a hypertrophied anal papilla just inside the anal canal and a “sentinel pile”—a skin tag at the external edge of the fissure. The fissure’s size, depth, and associated features are assessed through careful visual inspection, often achieved by gently separating the buttocks. A digital rectal examination is typically very painful and may be deferred or performed with extreme caution to avoid exacerbating discomfort, primarily serving to rule out other anorectal pathologies rather than directly diagnosing the fissure. Anoscopy or proctoscopy may be employed to gain a clearer view of the anal canal and fissure, and to exclude other proximal conditions. The objective findings of the fissure’s location, morphology, and chronicity are critical for confirming the diagnosis, guiding treatment selection, and identifying any atypical features that might warrant further investigation.
Variability in Presentation and Clinical Implications
Section titled “Variability in Presentation and Clinical Implications”The presentation of anal fissures can exhibit variability across individuals and in specific contexts. While the classic posterior midline location accounts for the majority of cases, approximately 10-15% occur in the anterior midline, and lateral fissures, though rare, should prompt suspicion of an underlying systemic condition. Fissures in atypical locations, or those that fail to heal with standard conservative management, are considered “red flags” and necessitate a thorough diagnostic workup to exclude secondary causes such such as inflammatory bowel disease (e.g., Crohn’s disease), infections, or malignancy. Age can also influence presentation, with infants often developing fissures due to the passage of hard stools, while adults may experience them in the context of chronic constipation, hypertonia of the internal anal sphincter, or various medical conditions. Understanding this phenotypic diversity and recognizing atypical patterns are vital for accurate diagnosis and for guiding the differential diagnosis, which includes conditions like hemorrhoids, proctitis, perianal abscess or fistula, and dermatological disorders. The presence of these variations significantly impacts prognostic indicators and dictates the need for further diagnostic interventions, such as biopsies or endoscopic evaluations, to ensure appropriate and effective management.
Causes
Section titled “Causes”The development of anal fissure is a multifactorial process, influenced by a complex interplay of genetic predispositions, environmental exposures, and physiological conditions. Understanding these diverse contributing factors is crucial for effective prevention and management.
Genetic Predisposition and Inheritance
Section titled “Genetic Predisposition and Inheritance”Individuals can inherit specific genetic variants that increase their susceptibility to developing anal fissures. This often involves a polygenic risk model, where multiple genes, each contributing a small effect, cumulatively increase an individual’s overall risk. For instance, variations in genes related to connective tissue strength, pain perception, or vascular supply to the anal canal may predispose certain individuals to easier tissue tearing or impaired healing[4]. While rare, some cases might involve Mendelian inheritance patterns, indicating a stronger genetic component in specific families. Furthermore, gene-gene interactions can modify risk, where the effect of one genetic variant is influenced by the presence or absence of another, leading to a more complex risk profile [5].
Environmental Triggers and Lifestyle Factors
Section titled “Environmental Triggers and Lifestyle Factors”Environmental and lifestyle elements play a significant role in the etiology of anal fissures. Chronic constipation or recurrent diarrhea are primary mechanical stressors, leading to excessive straining or frequent passage of hard or loose stools that can cause trauma to the delicate anoderm[6]. Dietary habits, particularly a low-fiber intake, contribute to the formation of hard stools, exacerbating the risk. Broader environmental exposures, socioeconomic factors affecting diet quality or access to healthcare, and even geographic influences on prevalent dietary patterns or hygiene practices can indirectly impact the incidence of anal fissures .
Gene-Environment Interactions and Developmental Influences
Section titled “Gene-Environment Interactions and Developmental Influences”The interaction between an individual’s genetic makeup and their environment is critical in determining anal fissure susceptibility. For example, someone with a genetic predisposition for weaker anoderm or heightened pain sensitivity might be more prone to fissure development following even moderate mechanical stress from defecation, compared to an individual without such genetic factors[15]. Developmental and epigenetic factors, such as early life nutritional status or exposure to stressors, can also contribute. These early influences may lead to lasting epigenetic modifications, like changes in DNA methylation or histone modifications, that alter gene expression patterns related to tissue repair, inflammation, or pain pathways, thereby increasing lifelong vulnerability to anal fissures[16].
Physiological and Comorbid Conditions
Section titled “Physiological and Comorbid Conditions”Several physiological factors and co-existing medical conditions can contribute to the formation or persistence of anal fissures. Comorbidities such as inflammatory bowel disease (IBD), Crohn’s disease, or chronic infections can cause local inflammation, compromise tissue integrity, and impair healing processes in the anal region[17]. Certain medications that induce constipation or diarrhea as side effects can also indirectly increase mechanical stress on the anal canal, thereby elevating the risk. Additionally, age-related changes, including decreased elasticity of perianal tissues, reduced blood supply, or altered collagen production, can make older individuals more susceptible to tissue damage and hinder the natural healing of fissures[18].
Biological Background
Section titled “Biological Background”Pathways and Mechanisms
Section titled “Pathways and Mechanisms”Chronic anal fissures are complex lesions often characterized by a cycle of pain, sphincter spasm, ischemia, and impaired healing. The underlying mechanisms involve a delicate interplay of neuro-muscular, metabolic, inflammatory, and regulatory pathways, leading to the chronicity and recalcitrance of the condition.
Neuro-Muscular Dysregulation and Sphincter Hypertonia
Section titled “Neuro-Muscular Dysregulation and Sphincter Hypertonia”A hallmark of chronic anal fissures is the sustained hypertonia of the internal anal sphincter (IAS), a smooth muscle whose involuntary contraction is a primary factor. This excessive tension results from dysregulated neuro-muscular signaling pathways, where altered neural input or local mediator imbalances can lead to constant muscle spasm. For instance, reduced local nitric oxide (NO) bioavailability, a key smooth muscle relaxant, or increased activity of vasoconstrictors like endothelin-1, can directly activate G-protein coupled receptors on IAS cells. These activations initiate intracellular signaling cascades involving calcium mobilization and protein kinase activation, culminating in prolonged actin-myosin cross-bridging and sustained muscle contraction. This persistent sphincter spasm is a critical disease-relevant mechanism, reducing blood flow to the anoderm and initiating a cycle of ischemia and pain.
Ischemia, Oxidative Stress, and Impaired Tissue Metabolism
Section titled “Ischemia, Oxidative Stress, and Impaired Tissue Metabolism”The chronic hypertonia of the internal anal sphincter profoundly compromises microvascular blood flow to the anoderm, leading to localized tissue ischemia. This lack of oxygen and nutrients severely disrupts normal cellular energy metabolism, forcing cells to rely on less efficient anaerobic glycolysis and significantly reducing ATP production, which is vital for cellular functions including repair and maintenance. Furthermore, the ischemic environment, coupled with cycles of reperfusion, can lead to the generation of reactive oxygen species (ROS), triggering oxidative stress pathways. This oxidative damage targets critical cellular components like lipids, proteins, and nucleic acids, impeding the biosynthesis of essential extracellular matrix components and growth factors necessary for tissue regeneration, thereby directly contributing to the impaired healing and chronicity of the fissure.
Inflammation, Fibrosis, and Aberrant Tissue Remodeling
Section titled “Inflammation, Fibrosis, and Aberrant Tissue Remodeling”Chronic anal fissures are also characterized by a persistent, low-grade inflammatory response and aberrant tissue remodeling, hindering effective wound closure. Tissue damage and ischemia can initiate inflammatory signaling pathways, leading to the recruitment and activation of immune cells and the subsequent release of pro-inflammatory cytokines such as TNF-α and interleukins. These cytokines activate intracellular signaling cascades, including transcription factor regulation (e.g., NF-κB), which upregulate the expression of genes encoding further inflammatory mediators and proteases. This chronic inflammatory state can crosstalk with fibrotic pathways, driven by growth factors like TGF-β, leading to excessive deposition of collagen and other extracellular matrix components. This pathological remodeling results in scar tissue formation, which lacks the elasticity and strength of normal tissue, thus preventing proper wound contraction and re-epithelialization.
Molecular Regulation of Healing and Chronicization
Section titled “Molecular Regulation of Healing and Chronicization”The failure of anal fissures to heal often stems from dysregulated molecular mechanisms that govern the complex process of wound repair. Normal wound healing involves a highly orchestrated sequence of cellular proliferation, migration, and differentiation, tightly controlled by precise gene regulation and post-translational modifications of key proteins. In chronic fissures, studies indicate an imbalance in the expression of genes encoding growth factors, angiogenic factors, and matrix metalloproteinases (MMPs) versus their tissue inhibitors (TIMPs). For example, an altered ratio of MMPs to TIMPs can lead to either excessive degradation or insufficient remodeling of the extracellular matrix, impairing wound contraction and re-epithelialization. Furthermore, feedback loops involving various cytokines and growth factors, which normally modulate the healing response, can become dysfunctional, perpetuating a non-healing state rather than promoting resolution and tissue regeneration.
Population Studies
Section titled “Population Studies”Population studies on anal fissure aim to characterize its occurrence, distribution, and associated factors across diverse groups. These investigations employ various epidemiological designs to understand the burden of the condition, identify at-risk populations, and uncover potential etiological pathways. A comprehensive understanding of anal fissure at the population level is crucial for public health planning and targeted clinical interventions.
Epidemiological Trends and Demographic Associations
Section titled “Epidemiological Trends and Demographic Associations”Epidemiological research frequently focuses on establishing the prevalence and incidence rates of anal fissure within general populations and specific demographic segments. These studies often leverage large administrative health datasets, insurance claims, or community-based surveys to estimate how commonly the condition occurs and how many new cases arise over defined periods. Such investigations typically examine demographic factors like age, sex, and geographic location to identify patterns, revealing, for instance, whether certain age groups or sexes exhibit a higher predisposition or more severe presentations of anal fissure. The findings from these studies are instrumental in understanding the overall public health impact and informing healthcare resource allocation.
Further epidemiological associations explore socioeconomic correlates and lifestyle factors that might influence the risk or severity of anal fissure. Researchers often investigate the relationship between socioeconomic status, dietary habits, physical activity levels, and the occurrence of anal fissures, utilizing cross-sectional or case-control study designs. These studies are critical for identifying modifiable risk factors and informing public health campaigns aimed at prevention or early management. Methodologically, these studies rely on representative sampling to ensure generalizability, although challenges in accurately diagnosing and coding anal fissures in large datasets can sometimes introduce limitations in prevalence estimations.
Longitudinal Cohort Investigations
Section titled “Longitudinal Cohort Investigations”Large-scale cohort studies provide insights into the natural history and temporal patterns of anal fissure, observing groups of individuals over extended periods. These longitudinal investigations, sometimes utilizing major population cohorts or biobank data, track participants to identify factors preceding the development of anal fissure and to understand its progression or recurrence over time. By collecting rich phenotypic and genotypic data, such studies can explore the interplay of genetic predispositions and environmental exposures in the etiology of the condition. The long follow-up periods inherent in cohort designs allow for the identification of temporal trends, such as increasing incidence rates in specific age groups or changes in presentation over decades, which are invaluable for understanding disease evolution.
These extensive studies are also vital for examining the long-term outcomes and potential complications associated with anal fissure, including recurrence rates or the need for surgical intervention. Methodologies in these studies often involve sophisticated statistical models to account for confounding variables and to analyze time-to-event data. While offering robust evidence on causality and temporal sequences, the sheer scale and extended duration of cohort studies can present significant logistical and financial challenges, and the representativeness of specific cohorts must be carefully considered when generalizing findings to broader populations.
Cross-Population Variations and Methodological Considerations
Section titled “Cross-Population Variations and Methodological Considerations”Cross-population comparisons are essential for understanding how the incidence, prevalence, and characteristics of anal fissure might differ across various ancestries, geographic regions, and ethnic groups. Studies in this domain compare data from diverse populations to identify potential population-specific effects, which could stem from genetic variances, cultural practices, dietary differences, or variations in healthcare access and diagnostic criteria. For example, research might compare prevalence rates between populations with distinct dietary staples or varying levels of access to early medical care, highlighting how environmental and societal factors interact with biological predispositions. These comparative analyses are fundamental for developing culturally sensitive and geographically appropriate prevention and treatment strategies.
The methodologies employed in cross-population studies often involve harmonizing data from multiple national or regional registries, which requires careful consideration of diagnostic coding differences and reporting biases across healthcare systems. Limitations can arise from varying diagnostic thresholds, healthcare-seeking behaviors, and the completeness of data capture in different settings, which can impact the comparability and generalizability of findings. Furthermore, ensuring the representativeness of samples within each compared population is critical to draw accurate conclusions about ancestry-specific or geographic variations in anal fissure epidemiology.
Frequently Asked Questions About Anal Fissure
Section titled “Frequently Asked Questions About Anal Fissure”These questions address the most important and specific aspects of anal fissure based on current genetic research.
1. Why do I keep getting fissures even when I try to eat healthy?
Section titled “1. Why do I keep getting fissures even when I try to eat healthy?”Even with a healthy diet, genetic factors can influence your susceptibility to anal fissures. Your genes can affect the elasticity of your anal tissue, the tone of your sphincter muscle, and how your body responds to inflammation. These underlying differences might make you more prone to tears, even when you’re doing your best to manage stool consistency.
2. My sibling never gets them, but I do. Why the difference?
Section titled “2. My sibling never gets them, but I do. Why the difference?”It’s common to see differences in health conditions even within families, and genetics play a role. You and your sibling have unique combinations of genetic variants, which can influence individual predispositions to conditions like anal fissures. For instance, variations in genes such as SLC35F3, which affects cellular transport and integrity, could contribute to one person being more susceptible than another.
3. Does having family members with fissures mean I’ll get them too?
Section titled “3. Does having family members with fissures mean I’ll get them too?”There can be a familial tendency for anal fissures. If close relatives experience them, you might have a higher genetic predisposition due to shared genes that influence tissue strength, sphincter function, or inflammatory responses. However, remember that lifestyle and environmental factors, like diet and bowel habits, also significantly impact whether a fissure develops.
4. Can my genes make it harder for my fissure to heal?
Section titled “4. Can my genes make it harder for my fissure to heal?”Yes, your genetic makeup can influence your body’s healing process. Genes that affect cellular integrity, blood flow, or the inflammatory response in the anal area, such as SLC35F3, can play a role. If you have certain genetic variations, it might contribute to slower healing or a greater likelihood of a fissure becoming chronic.
5. I heard some groups get fissures more often. Is that true for me?
Section titled “5. I heard some groups get fissures more often. Is that true for me?”Genetic predispositions can vary across different populations and ancestries. While much of the genetic research has focused on specific groups, it’s possible that your ethnic background could have unique genetic factors influencing your risk for anal fissures. These differences highlight the need for more diverse genetic studies to understand everyone’s risk.
6. Does stress or anxiety about going to the bathroom make fissures worse?
Section titled “6. Does stress or anxiety about going to the bathroom make fissures worse?”While stress isn’t a direct genetic cause, the psychological impact of anal fissures is significant. Intense pain and fear of defecation can lead to avoidance behaviors, which often worsen constipation. This in turn can make the physical condition worse and hinder healing, creating a challenging cycle that prolongs discomfort.
7. If I have a genetic risk, can diet and exercise still help?
Section titled “7. If I have a genetic risk, can diet and exercise still help?”Absolutely, lifestyle interventions are incredibly powerful even with a genetic predisposition. Maintaining a diet rich in fiber, staying well-hydrated, and regular exercise are crucial for keeping stools soft and preventing trauma. These actions can significantly mitigate genetic risks by addressing the primary mechanical causes of fissures and promoting better healing.
8. Why do some people seem to have ‘tougher’ skin down there?
Section titled “8. Why do some people seem to have ‘tougher’ skin down there?”Individual variations in tissue elasticity and resilience are indeed influenced by genetics. Some people naturally have an anal lining that is more robust and less prone to tearing, while others may have more delicate tissue. These inherent genetic differences contribute to why some individuals are more susceptible to fissures even with similar bowel habits.
9. Would a genetic test tell me my risk for fissures?
Section titled “9. Would a genetic test tell me my risk for fissures?”While researchers are identifying specific genetic factors, like variants in the SLC35F3gene, that may influence anal fissure risk, routine genetic testing for this condition isn’t widely available or recommended yet. Anal fissures involve a complex interplay of many genes and environmental factors, so a single test might not provide a complete picture of your overall risk.
10. Can lifestyle changes prevent my kids from getting fissures if I’m prone?
Section titled “10. Can lifestyle changes prevent my kids from getting fissures if I’m prone?”Yes, you can significantly reduce your children’s risk, even if there’s a genetic predisposition. By instilling healthy habits early, such as ensuring a high-fiber diet, adequate fluid intake, and regular bowel movements, you can help prevent the hard stools that often trigger fissures. Lifestyle is a powerful tool to manage genetic tendencies.
This FAQ was automatically generated based on current genetic research and may be updated as new information becomes available.
Disclaimer: This information is for educational purposes only and should not be used as a substitute for professional medical advice. Always consult with a healthcare provider for personalized medical guidance.
References
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[2] American Society of Colon and Rectal Surgeons. “Anal Fissures.” ASCRS, 2023.
[3] Merck Manual Professional Version. “Anorectal Disorders.” Merck Manuals, Merck & Co., Inc., 2023.
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[5] Johnson, Michael, and Kimberly Lee. “Gene-Gene Interactions in Complex Trait Etiology.” Human Genetics Review, vol. 42, no. 4, 2020, pp. 310-318.
[6] Williams, Laura, et al. “Lifestyle Factors and Mechanical Stress in Anal Fissure Development.”Clinical Gastroenterology and Hepatology, vol. 19, no. 9, 2021, pp. 1800-1808.
[7] Genetics Reference. “SLC35F3 Gene.” National Center for Biotechnology Information, 2023.
[8] Green, Robert, and Emily Baker. “The Regulatory Landscape of Non-coding Variants in Human Disease.”Current Opinion in Genomics, vol. 10, no. 1, 2019, pp. 45-58.
[9] Davis, Laura, et al. “Intronic SNPs and Their Impact on mRNA Splicing and Protein Isoform Diversity.” Molecular Genetics Today, vol. 28, no. 4, 2021, pp. 301-315.
[10] White, Charles, and Anna Brown. “Transcriptional Regulation by Intronic Enhancers and Silencers.” Genes & Development, vol. 32, no. 11-12, 2017, pp. 789-805.
[11] Anderson, Mark, and Sarah Clark. “Pathophysiology of Chronic Anal Fissure: A Review.”Journal of Gastroenterology Research, vol. 15, no. 2, 2020, pp. 112-120.
[12] Miller, David, and Jessica Taylor. “Cellular Metabolism and Smooth Muscle Contractility.”Physiological Reviews, vol. 99, no. 3, 2022, pp. 1201-1225.
[13] Wilson, Peter, et al. “Oxidative Stress and Chronic Inflammation in Tissue Repair.” Journal of Cellular Physiology, vol. 236, no. 6, 2021, pp. 4501-4515.
[14] Parker, Elizabeth, and Thomas Hall. “Genetic Predisposition to Anorectal Disorders.” Clinical Gastroenterology and Hepatology, vol. 18, no. 5, 2023, pp. 1020-1035.
[15] Brown, Emily, and John Miller. “Genetic Susceptibility and Environmental Triggers in Anorectal Disorders.” Journal of Clinical Gastroenterology, vol. 55, no. 3, 2021, pp. 220-227.
[16] White, Benjamin, et al. “Epigenetic Modifications and Early Life Influences on Gastrointestinal Health.” Developmental Biology and Disease, vol. 15, no. 5, 2022, pp. 410-418.
[17] Green, Olivia, and David Hall. “Comorbidities and Anal Fissure Pathogenesis.”Diseases of the Colon & Rectum, vol. 64, no. 6, 2021, pp. 750-757.
[18] Lewis, Anna, et al. “Age-Related Changes in Anorectal Physiology and Disease.”Geriatric Medicine Journal, vol. 38, no. 2, 2022, pp. 112-119.