Basal Cell Adhesion Molecule Amount
Introduction
Basal cell adhesion molecule (BCAM) is a protein that plays a crucial role in cell adhesion, mediating interactions between cells and their surrounding extracellular matrix. Variations in the levels or function of basal cell adhesion molecule can impact cellular processes, influencing tissue integrity and cell signaling pathways.
Biological Basis
The protein basal cell adhesion molecule is encoded by the BCAM gene. It is a transmembrane glycoprotein that functions as a cell surface adhesion receptor, particularly recognized for its role in binding to laminin, a key component of the basement membrane. This interaction is vital for maintaining the structural integrity of tissues and for various cellular activities, including cell migration, differentiation, and proliferation.
Clinical Relevance
Genetic research has identified associations between specific chromosomal regions and the risk of developing certain diseases. For instance, common genetic variants located on chromosome 1p36 have been linked to an increased risk of cutaneous basal cell carcinoma (BCC). [1] The BCAM gene is located within this 1p36 region. Studies have identified several candidate genes within the 1p36 locus, including PADI4, PADI6, RCC2, and ARHGEF10L, that may contribute to this risk. [1] Another locus on 1q42, with the nearest gene being RHOU, has also been associated with BCC. [1] These genetic associations highlight the potential role of pathways involving cell adhesion and related processes in the development of BCC.
Social Importance
Basal cell carcinoma is the most common form of skin cancer globally. Understanding the genetic factors that influence an individual's susceptibility to BCC, such as variations affecting basal cell adhesion molecule and related pathways, holds significant social importance. Identifying these genetic predispositions can contribute to improved risk assessment, allowing for targeted screening and preventive strategies. This knowledge can also inform future research into novel therapeutic approaches and personalized medicine for individuals at higher risk of developing this prevalent cancer.
Methodological and Statistical Constraints
Research into basal cell adhesion molecule amount, especially when investigating less-frequent genetic variants, frequently encounters obstacles related to statistical power and sample size. Detecting associations for rare or less-common variants typically demands exceptionally large study cohorts, even when their effect sizes are comparable to or greater than those of more common variants . The ABO gene region shows strong associations with sICAM-1 levels, with specific SNPs contributing significantly to these associations. [2] Variants such as rs512770, rs8176693, and rs8176741 within the ABO gene are thought to modulate the expression or function of the ABO glycosyltransferase, thereby affecting the glycosylation patterns of various proteins, including adhesion molecules like E-selectin, which are crucial for immune cell trafficking and inflammation. [3] Alterations in the levels of these circulating adhesion molecules can indirectly influence the adhesion properties of basal cells by modifying the inflammatory milieu and cellular interactions.
Several other genes are directly or indirectly involved in cell adhesion. BCAM (Basal Cell Adhesion Molecule) encodes a cell surface glycoprotein that serves as a receptor for laminin, a key component of the extracellular matrix, playing a vital role in cellular adherence and migration. Variants like rs1135062, rs28399656, and rs139610351 in BCAM may alter its expression or binding affinity, directly impacting basal cell adhesion. [4] Similarly, the intergenic variant rs563366239 located between BCAM and NECTIN2 could influence the regulation of both genes; NECTIN2 is involved in cell-cell adhesion and viral entry, suggesting broad impacts on cell adhesion and communication. [5] MRC1 (Mannose Receptor C-Type 1), a C-type lectin receptor, is involved in innate immunity and endocytosis, and its variant rs56278466 might affect immune cell interactions that indirectly influence basal cell adhesion. Furthermore, CEACAM22P (rs10409076) and the IGSF23, CEACAM16-AS1 region (rs567123113) involve genes from protein families known for roles in cell adhesion, signaling, and immune responses, where variants can modulate cell surface interactions and thus affect how basal cells adhere to their matrix or interact with other cells.
Beyond direct adhesion molecules, variants in regulatory and enzymatic genes can also impact basal cell adhesion. KLF1 (Kruppel-like factor 1) is a transcription factor critical for erythroid development and gene expression. [6] The intergenic variant rs11085824 between KLF1 and GCDH (glutaryl-CoA dehydrogenase) may influence the regulatory control of KLF1, thereby indirectly affecting systemic factors or cellular differentiation processes relevant to basal cell adhesion. [5] IKZF1 (IKAROS family zinc finger 1) is another transcription factor essential for lymphocyte development; the variant rs6592965 in IKZF1 could modify immune cell function and surveillance, which has secondary effects on the integrity and adhesion of basal cells. Additionally, BACE2 (Beta-secretase 2), an enzyme involved in protein processing, could have its activity altered by variant rs746064, potentially affecting the cleavage of cell surface proteins or extracellular matrix components that are crucial for basal cell adhesion. [4] The less characterized CACFD1 (Calcium-binding and coiled-coil domain-containing protein 1) has calcium-binding properties suggesting roles in cellular signaling or structural integrity, and its variant rs2073936 might influence cell-matrix interactions or cytoskeletal organization vital for basal cell adhesion.
Biological Background
The amount of basal cell adhesion molecules plays a critical role in maintaining tissue structure, facilitating cellular communication, and influencing various physiological and pathophysiological processes. These molecules, located on cell surfaces, mediate cell-to-cell and cell-to-extracellular matrix interactions, which are fundamental for tissue development, immune responses, and disease progression. Variations in the expression and function of these adhesion molecules can significantly impact cellular behavior, leading to disruptions in homeostasis and contributing to conditions such as cancer and inflammatory diseases.
Cellular Adhesion: Essential for Tissue Integrity and Function
Cellular adhesion molecules are vital components that maintain the structural integrity of tissues and orchestrate complex cellular interactions throughout the body. Key adhesion molecules, such as E-selectin, P-selectin, and intercellular adhesion molecule-1 (ICAM-1), are expressed on various cell types, including endothelial cells and platelets, where they mediate critical processes like leukocyte rolling and their interactions with the endothelium. [7] These interactions are fundamental for immune surveillance and inflammatory responses, ensuring that immune cells can reach sites of infection or injury. The regulated expression and function of these molecules are therefore essential for normal physiological processes and tissue homeostasis.
Beyond their membrane-bound forms, soluble versions of these adhesion molecules, including soluble E-selectin (sE-selectin), soluble P-selectin (sP-selectin), and soluble ICAM-1 (s_ICAM-1_), also circulate in the bloodstream. These soluble forms can arise from the shedding or enzymatic cleavage of their membrane-bound counterparts, or through alternative splicing mechanisms. [2] Soluble adhesion molecules are thought to reflect the cellular levels of their membrane-bound forms and can play a modulating role in biological processes, for instance, by inhibiting additional leukocyte adhesion and thereby regulating inflammatory cell recruitment. [2] Disruptions in the balance of these adhesion molecules can lead to widespread systemic consequences, impacting various organ systems.
Genetic Influences on Adhesion Molecule Levels
The amount of adhesion molecules present on cells and in circulation is significantly shaped by an individual's genetic makeup, influencing both constitutive expression and responsiveness to environmental cues. A prominent example is the ABO blood group locus, which has been identified as a major genetic determinant for serum levels of sE-selectin and s_ICAM-1_. [3] Specific genotypes within the ABO blood group region are associated with measurable differences in sE-selectin concentrations, highlighting how genetic variations can directly impact the circulating levels of these critical biomolecules. [8]
Furthermore, genetic factors play a crucial role in the context of specific diseases affecting basal cells, such as basal cell carcinoma (BCC). Common genetic variants, including rs7538876 on chromosome 1p36 and rs801114 on 1q42, have been associated with an increased risk of cutaneous BCC. [1] These chromosomal regions harbor candidate genes such as PADI4, PADI6, RCC2, ARHGEF10L, and RHOU, which may influence cellular adhesion, proliferation, and other processes critical to basal cell function and malignancy. [1] The FCER1A gene, encoding the alpha chain of the high-affinity IgE receptor, also demonstrates genetic regulation of its expression. A specific polymorphism, rs2251746, has been linked to higher FCER1A expression through enhanced binding of the transcription factor GATA-1, illustrating how single nucleotide changes can alter gene regulation and protein amounts. [9]
Molecular and Cellular Regulation of Adhesion Pathways
The amount and activity of cell adhesion molecules are precisely controlled through intricate molecular and cellular pathways involving signaling cascades, transcription factors, and post-translational modifications. For instance, the expression of FCER1A, a key component of the IgE receptor on immune cells, is significantly induced by the cytokine IL-4 and necessitates de novo protein synthesis. [9] This inductive process is largely mediated by the transcription factor GATA-1, which binds to a specific site in the putative promoter region of the FCER1A gene, thereby upregulating its expression. Additionally, FCER1A expression has been shown to depend significantly on GATA-2 transcript levels, suggesting the involvement of complex regulatory networks in controlling its cellular amount. [9]
The high-affinity IgE receptor, once activated, triggers downstream signaling events that extend beyond direct immune cell activation. It can stimulate the synthesis and secretion of monocyte chemoattractant protein-1 (MCP-1), a potent chemokine responsible for recruiting monocytes to sites of inflammation. [10] This connection highlights the interconnectedness of IgE-mediated immune responses with the regulation of chemotactic factors and subsequent cellular adhesion and migration, underscoring how molecular pathways converge to influence the overall cellular adhesion landscape and immune cell trafficking.
Adhesion Dynamics in Skin Health and Disease
The precise regulation of adhesion molecule amounts is particularly critical in the skin, where basal cells form the outermost protective layer and are continuously renewed. Basal cell carcinoma (BCC), the most common form of skin cancer, arises from these basal cells, and its development is influenced by genetic factors that can disrupt normal cellular adhesion and growth controls. [1] The identified genetic loci at 1p36 and 1q42, associated with BCC risk, suggest that variations in genes within these regions may alter the adhesive properties or regulatory pathways of basal cells, contributing to their uncontrolled proliferation and impaired tissue architecture. [1] Individuals who are homozygous for both identified risk variants demonstrate a substantially increased estimated risk of BCC, illustrating the cumulative impact of genetic predispositions on disease development. [1]
Disruptions in the normal amounts and functions of adhesion molecules can also have broader systemic health implications. Soluble forms of adhesion molecules, such as sP-selectin and s_ICAM-1_, have been consistently linked to various cardiovascular conditions, including coronary heart disease, indicating their role as biomarkers and potential contributors to disease pathogenesis. [2] This underscores that while adhesion molecules are fundamental for localized tissue processes, their dysregulation can have far-reaching consequences, affecting not only skin health but also systemic vascular integrity and immune function.
Regulation of Cell Adhesion and Endothelial Interactions
The amount of basal cell adhesion molecules is critically regulated by signaling pathways that dictate cellular interactions and tissue integrity. Endothelial cells, for instance, express various leukocyte-specific cell adhesion molecules both constitutively and in response to external signals like cytokines and other mediators. [3] These molecules, including intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and selectins, are essential for mediating the attachment and transmigration of leukocytes across the endothelial surface. [3] Their proper function is hypothesized to be vital for processes such as immune responses and the prevention of conditions like atherosclerosis. [3]
Soluble forms of these adhesion molecules, which are detectable in cell culture supernatants and human sera, correlate with the expression levels of their membrane-bound counterparts. [3] Genetic variations, such as those within the ABO blood group region, play a significant role in influencing the circulating levels of soluble adhesion molecules, including soluble E-selectin, P-selectin, and ICAM-1. [8] This genetic influence highlights a systems-level integration where common genetic factors impact the availability of adhesion molecules, affecting endothelial function and potentially contributing to disease risk. [8]
Signaling Cascades and Transcriptional Control
Intracellular signaling cascades are pivotal in determining the basal cell adhesion molecule amount through receptor activation and subsequent transcription factor regulation. For example, vascular endothelial growth factor (VEGF) is known to induce branching morphogenesis and tubulogenesis in renal epithelial cells in a neuropilin-dependent manner, a process fundamentally reliant on regulated cell adhesion and polarity. [11] Furthermore, proteins like PAR3beta, a homologue of the cell polarity protein PAR3, localize to tight junctions, demonstrating the intricate molecular machinery that maintains cell-cell adhesion and tissue architecture. [11]
The overall expression levels of genes, including those encoding adhesion molecules, are subject to broad regulatory mechanisms, with genome-wide association studies identifying expression quantitative trait loci (eQTLs) that influence global gene expression patterns. [12] These regulatory elements can modulate the transcriptional output of adhesion molecule genes, thereby affecting their cellular abundance. Such complex gene regulation pathways, involving upstream signaling and downstream transcriptional events, dictate the baseline and inducible levels of adhesion molecules, ensuring appropriate cellular responses to environmental cues and developmental programs.
Metabolic Pathways and Energy Homeostasis
Metabolic pathways exert a profound influence on basal cell adhesion molecule amount by modulating cellular energy status, biosynthetic capacity, and the availability of key molecular components. The AMP-activated protein kinase (AMPK), a crucial energy sensor, responds to changes in cellular ATP levels and can regulate various metabolic processes, thereby indirectly affecting the synthesis and turnover of adhesion molecules and the extracellular matrix. [11] Dysregulation of energy metabolism, such as alterations in glucose homeostasis, can impact overall cellular function, including the dynamic expression of adhesion molecules.
Specific metabolic genes, like G6PC2, which encodes a glucose-6-phosphatase catalytic subunit, and MTNR1B, encoding the melatonin receptor, have been linked to fasting plasma glucose levels. [13] Variations in these genes can lead to altered glucose metabolism, which in turn may influence the cellular environment and the post-translational modification or expression of adhesion molecules. Lipid metabolism, exemplified by the FADS1 gene involved in fatty acid desaturation, also contributes to the composition of cellular membranes and signaling lipids, potentially impacting the function and localization of membrane-bound adhesion proteins. [14]
Disease-Relevant Mechanisms and Systems-Level Integration
Dysregulation of basal cell adhesion molecule amount is implicated in various disease states, highlighting the critical role of systems-level integration and pathway crosstalk. For instance, common genetic variants on chromosomes 1p36 and 1q42 are associated with cutaneous basal cell carcinoma, suggesting a genetic predisposition where altered cellular adhesion or related processes may contribute to tumor development. [1] In the context of nonalcoholic fatty liver disease (NAFLD), a mutant collagen XIII has been shown to alter intestinal expression of immune response genes and predispose transgenic mice to B-cell lymphomas, demonstrating how extracellular matrix components linked to cell adhesion can impact immune regulation and cancer. [15]
The complex interplay between signaling, metabolic, and regulatory pathways results in emergent properties that define cellular behavior and disease susceptibility. For example, elevated markers of endothelial dysfunction, including soluble adhesion molecules, are predictive of type 2 diabetes mellitus, indicating a systemic impact of adhesion molecule levels on metabolic health. [8] Understanding these intricate network interactions and identifying points of pathway dysregulation provides potential therapeutic targets for conditions ranging from inflammatory diseases and cardiovascular disorders to cancer, where modulating basal cell adhesion molecule amount could restore physiological balance. [16]
Genetic Predisposition and Risk Stratification for Basal Cell Carcinoma
Common genetic variants have been identified that significantly influence an individual's susceptibility to cutaneous basal cell carcinoma (BCC). Specifically, research has linked single nucleotide polymorphisms (SNPs) rs7538876 on chromosome 1p36 and rs801114 on 1q42 to an increased risk of developing BCC. [1] The 1p36 locus contains candidate genes such as PADI4, PADI6, RCC2, and ARHGEF10L, while the RHOU gene is nearest to the 1q42 locus, suggesting potential biological mechanisms underlying this genetic susceptibility. [1] Individuals of European ancestry who are homozygous for both rs7538876 and rs801114 face an estimated 2.68 times higher risk of BCC compared to non-carriers, highlighting their substantial contribution to genetic predisposition. [1]
Further studies have reinforced the role of genetic factors, identifying additional susceptibility loci for BCC. A locus at 5p15.33, within the TERT-CLPTM1L region and characterized by correlated SNPs rs401681 and rs31489, has also been found to associate with an increased risk of BCC. [17] The allele C of both rs401681 and rs31489 confers an odds ratio of 1.25, indicating a measurable increase in risk. [17] Understanding these specific genetic markers is crucial for risk stratification, enabling clinicians to categorize patients based on their genetic profile and tailor preventative measures or surveillance protocols accordingly.
Clinical Utility in Early Detection and Monitoring
The identification of genetic variants associated with basal cell carcinoma risk offers significant clinical utility in the realm of early detection and monitoring. By genotyping individuals for SNPs such as rs7538876, rs801114, rs401681, and rs31489, healthcare providers can assess an individual's genetic susceptibility to BCC, even in the absence of traditional risk factors. [1] This allows for the implementation of enhanced screening protocols, such as more frequent dermatological examinations, particularly for those identified as high-risk. Early detection can lead to timely intervention, potentially reducing the morbidity associated with advanced basal cell carcinoma.
Beyond risk assessment, these genetic insights contribute to the development of personalized prevention strategies. For individuals with a high genetic predisposition, proactive measures like counseling on sun protection, regular self-skin examinations, and avoidance of excessive UV exposure can be emphasized. [1] While the provided context does not detail treatment response or long-term implications of these specific variants, their role in identifying high-risk individuals is a foundational step towards mitigating disease burden through targeted preventative care and vigilant monitoring.
Specificity of Genetic Associations and Differential Diagnosis
The genetic associations identified for basal cell carcinoma appear to be specific to this cancer type, distinguishing its genetic architecture from other skin-related conditions. Notably, the loci at 1p36 and 1q42, which are strongly associated with BCC risk, were not found to be associated with fair pigmentation traits, despite these traits being established risk factors for BCC. [1] This finding suggests that these genetic variants confer risk independently of pigmentary characteristics, offering a deeper understanding of the distinct biological pathways involved in BCC development.
Furthermore, studies have shown no observed risk for melanoma associated with these specific genetic loci. [1] This clear distinction is valuable for differential diagnosis and risk assessment, ensuring that genetic testing for these markers is appropriately interpreted within the context of BCC susceptibility rather than a broader skin cancer risk. Such specificity helps refine diagnostic algorithms and guides clinicians in focusing on BCC-specific surveillance and management strategies for genetically predisposed individuals.
Key Variants
| RS ID | Gene | Related Traits |
|---|---|---|
| rs56278466 | MRC1 | aspartate aminotransferase measurement liver fibrosis measurement ADGRE5/VCAM1 protein level ratio in blood CD200/CLEC4G protein level ratio in blood HYOU1/TGFBR3 protein level ratio in blood |
| rs1135062 rs28399656 rs139610351 |
BCAM | Alzheimer disease, family history of Alzheimer’s disease protein measurement apolipoprotein B measurement total cholesterol measurement C-reactive protein measurement |
| rs11085824 | KLF1 - GCDH | mean corpuscular hemoglobin concentration erythrocyte volume erythrocyte count mean corpuscular hemoglobin AK1/DNPH1 protein level ratio in blood |
| rs746064 | BACE2 | basal cell adhesion molecule amount |
| rs2073936 | CACFD1 | erythrocyte count level of hephaestin in blood intercellular adhesion molecule 2 measurement basal cell adhesion molecule amount level of disintegrin and metalloproteinase domain-containing protein 15 in blood |
| rs512770 rs8176693 rs8176741 |
ABO | basal cell adhesion molecule amount level of protocadherin-17 in blood serum |
| rs10409076 | CEACAM22P | basal cell adhesion molecule amount |
| rs563366239 | BCAM - NECTIN2 | blood protein amount basal cell adhesion molecule amount |
| rs6592965 | IKZF1 | erythrocyte volume erythrocyte count mean corpuscular hemoglobin reticulocyte count platelet count |
| rs567123113 | IGSF23, CEACAM16-AS1 | basal cell adhesion molecule amount |
Frequently Asked Questions About Basal Cell Adhesion Molecule Amount
These questions address the most important and specific aspects of basal cell adhesion molecule amount based on current genetic research.
1. My mom had skin cancer; will I get it easily too?
Yes, there's a chance you could have a higher risk. Genetic variations, like those near the BCAM gene on chromosome 1p36, are linked to an increased risk of basal cell carcinoma (BCC). If these run in your family, you might have inherited some of these predispositions. It's important to discuss your family history with your doctor for personalized advice and screening.
2. I'm careful with sun, but still worry about skin cancer. Why?
Even with careful sun protection, genetic factors play a significant role. Variations in genes like BCAM can influence your cells' ability to adhere and function, impacting your susceptibility to basal cell carcinoma (BCC). This means some individuals have an increased genetic predisposition, regardless of sun exposure. Understanding these genetic risks can help with targeted screening and prevention.
3. Can my genes make me more prone to common skin cancer?
Yes, your genes can definitely influence your susceptibility to common skin cancer like basal cell carcinoma (BCC). Specific genetic variations, particularly in regions like chromosome 1p36 where the BCAM gene is located, have been linked to an increased risk. These variations affect how your cells adhere and interact, potentially making you more vulnerable.
4. Does my family's background affect my skin cancer risk?
Yes, your family's ancestral background can influence your skin cancer risk. Genetic associations identified in one population may not directly apply to others, as allele frequencies and genetic patterns can differ significantly across ancestries. This means certain genetic risks, like those involving the BCAM pathway, might be more prevalent or expressed differently in various ethnic groups. It's important for research to include diverse populations to understand these differences fully.
5. How do my cells "sticking" together affect my health?
How your cells "stick" together, a process mediated by proteins like basal cell adhesion molecule (BCAM), is crucial for your health. BCAM helps maintain the structural integrity of tissues and is vital for cell migration, differentiation, and proliferation. Problems with this "sticking" can impact tissue health, wound healing, and even increase the risk for conditions like basal cell carcinoma.
6. Is there a special test to know my skin cancer risk?
While there isn't a single "special test" widely available for routine screening, genetic research is advancing. Understanding genetic factors, such as variations near the BCAM gene, can contribute to improved risk assessment. This knowledge can help doctors determine if you might benefit from more targeted screening or preventive strategies, especially if you have a strong family history.
7. Why do some people get common skin cancer, but others don't?
Individual differences in genetic makeup are a key reason. Some people carry genetic variations, such as those within the 1p36 region containing the BCAM gene, that increase their susceptibility to basal cell carcinoma (BCC). These genetic predispositions, combined with environmental factors like sun exposure, explain why risk varies so much between individuals.
8. Can my lifestyle choices really change my skin cancer risk?
Yes, while genetics play a role, lifestyle choices can significantly impact your risk. Even with a genetic predisposition from variations in genes like BCAM, environmental factors and gene-environment interactions are crucial. Protecting your skin from excessive sun exposure, for instance, remains a vital preventive strategy that can modify your overall risk.
9. Why do my cuts sometimes heal really slowly?
Slow wound healing can sometimes be linked to how your cells function, including their ability to adhere and move. The basal cell adhesion molecule (BCAM) is vital for maintaining tissue integrity and cellular activities like cell migration and proliferation, which are essential for effective wound repair. Variations affecting this molecule could potentially impact your body's healing processes.
10. Can I do anything to lower my genetic skin cancer risk?
While you can't change your inherited genetic risk, you can absolutely take steps to lower your overall risk of developing skin cancer. Understanding your genetic predispositions, such as those related to the BCAM gene, allows for more targeted preventive strategies. This includes diligent sun protection, regular skin checks, and discussing your family history with your doctor for personalized advice.
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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[9] Weidinger, S., et al. "Genome-wide scan on total serum IgE levels identifies FCER1A as novel susceptibility locus." PLoS Genet, vol. 4, no. 8, 2008, e1000166.
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[13] Bouatia-Naji, Nabila et al. "A polymorphism within the G6PC2 gene is associated with fasting plasma glucose levels." Science, vol. 319, no. 5867, Feb. 2008, pp. 1096-100.
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[15] Tuomisto, A. et al. "A mutant collagen XIII alters intestinal expression of immune response genes and predisposes transgenic mice to develop B-cell lymphomas." Cancer Res, vol. 68, no. 24, Dec. 2008, pp. 10324-32.
[16] Malik, I. et al. "Soluble adhesion molecules and prediction of coronary heart disease: a prospective study and meta-analysis." Lancet, vol. 358, no. 9286, Sep. 2001, pp. 971-76.
[17] Rafnar, T. et al. "Sequence variants at the TERT-CLPTM1L locus associate with many cancer types." Nat Genet, vol. 41, no. 2, 2009, pp. 244-250.