title: Variants in the CD36 gene associate with the metabolic syndrome and high-density lipoprotein cholesterol.
abstract: 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.
authors.affiliation: Department of Medicine, Center for Human Nutrition, Division of Biostatistics, Washington University School of Medicine, St Louis, MO 63110, USA. lgregory@im.wustl.edu
authors.forename: Latisha
authors.initials: L
authors.lastname: Love-Gregory
authors.forename: Richard
authors.initials: R
authors.lastname: Sherva
authors.forename: Lingwei
authors.initials: L
authors.lastname: Sun
authors.forename: Jon
authors.initials: J
authors.lastname: Wasson
authors.forename: Timothy
authors.initials: T
authors.lastname: Schappe
authors.forename: Alessandro
authors.initials: A
authors.lastname: Doria
authors.forename: D C
authors.initials: DC
authors.lastname: Rao
authors.forename: Steven C
authors.initials: SC
authors.lastname: Hunt
authors.forename: Samuel
authors.initials: S
authors.lastname: Klein
authors.forename: Rosalind J
authors.initials: RJ
authors.lastname: Neuman
authors.forename: M Alan
authors.initials: MA
authors.lastname: Permutt
authors.forename: Nada A
authors.initials: NA
authors.lastname: Abumrad
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D018955:CD36 Antigens / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014481:United States
chemical_list: D018955:CD36 Antigens; D008076:Cholesterol, HDL