Loci Related to Metabolic-Syndrome Pathways Including LEPR,HNF1A, IL6R, and GCKR Associate with Plasma C-Reactive Protein: The Women's Genome Health Study
| Autor: | Alex Parker, Jacqueline S. Danik, Joseph P. Miletich, David M Kwiatkowski, Julie E. Buring, Guillaume Paré, Nancy R. Cook, Robert Y.L. Zee, Daniel I. Chasman, Paul M. Ridker |
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| Rok vydání: | 2008 |
| Předmět: |
medicine.medical_specialty
Myocardial Infarction Single-nucleotide polymorphism Locus (genetics) Biology Polymorphism Single Nucleotide Plasma Insulin resistance Report Internal medicine Diabetes mellitus Genetics medicine Humans Genetics(clinical) Genetics (clinical) Inflammation Metabolic Syndrome Leptin receptor Genome Human C-reactive protein medicine.disease HNF1A Stroke C-Reactive Protein Endocrinology Diabetes Mellitus Type 2 biology.protein Female Insulin Resistance Metabolic syndrome |
| Zdroj: | The American Journal of Human Genetics. 82:1185-1192 |
| ISSN: | 0002-9297 |
| DOI: | 10.1016/j.ajhg.2008.03.015 |
| Popis: | Although elevated levels of C-reactive protein (CRP) independently predict increased risk of development of metabolic syndrome, diabetes, myocardial infarction, and stroke, comprehensive analysis of the influence of genetic variation on CRP is not available. To address this issue, we performed a genome-wide association study among 6345 apparently healthy women in which we evaluated 336,108 SNPs as potential determinants of plasma CRP concentration. Overall, seven loci that associate with plasma CRP at levels achieving genome-wide statistical significance were found (range of p values for lead SNPs within the seven loci: 1.9 x 10(-)(8) to 6.2 x 10(-)(28)). Two of these loci (GCKR and HNF1A) are suspected or known to be associated with maturity-onset diabetes of the young, one is a gene-desert region on 12q23.2, and the remaining four loci are in or near the leptin receptor protein gene, the apolipoprotein E gene, the interleukin-6 receptor protein gene, or the CRP gene itself. The protein products of six of these seven loci are directly involved in metabolic syndrome, insulin resistance, beta cell function, weight homeostasis, and/or premature atherothrombosis. Thus, common variation in several genes involved in metabolic and inflammatory regulation have significant effects on CRP levels, consistent with CRP's identification as a useful biomarker of risk for incident vascular disease and diabetes. |
| Databáze: | OpenAIRE |
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