Journal
HUMAN MOLECULAR GENETICS
Volume 17, Issue 11, Pages 1695-1704Publisher
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddn060
Keywords
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Funding
- NHLBI NIH HHS [U10 HL054471, U10 HL054496, U10 HL54515, U10 HL54496, U10 HL054472-05, U10 HL54495, U10 HL54509, U10 HL54473, U10 HL054496-05, U10 HL54471, U10 HL054509-05, U10 HL054471-05, U10 HL054495-05, U10 HL054515-05, U10 HL54472, U10 HL054473, U10 HL54497, U10 HL054472, U10 HL054473-05, U10 HL054509, U10 HL054497-05] Funding Source: Medline
- NIDDK NIH HHS [P30 DK056341, P30 DK056341-08, R01 DK060022, R37 DK016746-35, DK56351, R37 DK016746, R01 DK060022-07, R01 DK033301, R01 DK60022] Funding Source: Medline
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A region along chromosome 7q was recently linked to components of the metabolic syndrome (MetS) in several genome-wide linkage studies. Within this region, the CD36 gene, which encodes a membrane receptor for long-chain fatty acids and lipoproteins, is a potentially important candidate. CD36 has been documented to play an important role in fatty acid metabolism in vivo and subsequently may be involved in the etiology of the MetS. The protein also impacts survival to malaria and the influence of natural selection has resulted in high CD36 genetic variability in populations of African descent. We evaluated 36 tag SNPs across CD36 in the HyperGen population sample of 2020 African-Americans for impact on the MetS and its quantitative traits. Five SNPs associated with increased odds for the MetS [P = 0.0027-0.03, odds ratio (OR) = 1.3-1.4]. Coding SNP, rs3211938, previously shown to influence malaria susceptibility, is documented to result in CD36 deficiency in a homozygous subject. This SNP conferred protection against the MetS (P = 0.0012, OR = 0.61, 95%CI: 0.46-0.82), increased high-density lipoprotein cholesterol, HDL-C (P = 0.00018) and decreased triglycerides (P = 0.0059). Fifteen additional SNPs associated with HDL-C (P = 0.0028-0.044). We conclude that CD36 variants may impact MetS pathophysiology and HDL metabolism, both predictors of the risk of heart disease and type 2 diabetes.
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