TY - JOUR
T1 - Variants in the CD36 gene associate with the metabolic syndrome and high-density lipoprotein cholesterol
AU - Love-Gregory, Latisha
AU - Sherva, Richard
AU - Sun, Lingwei
AU - Wasson, Jon
AU - Schappe, Timothy
AU - Doria, Alessandro
AU - Rao, D. C.
AU - Hunt, Steven C.
AU - Klein, Samuel
AU - Neuman, Rosalind J.
AU - Permutt, M. Alan
AU - Abumrad, Nada A.
N1 - Funding Information:
National Institutes of Health (R01 DK60022, R37 DK016746); Washington University Clinical Nutrition Research Unit (DK56351). The HyperGEN network of the NHLBI Family Blood Pressure Program was funded by cooperative agreements (U10): HL54471, HL54472, HL54473, HL54495, HL54496, HL54497, HL54509, HL54515.
PY - 2008/6
Y1 - 2008/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=44349152442&partnerID=8YFLogxK
U2 - 10.1093/hmg/ddn060
DO - 10.1093/hmg/ddn060
M3 - Article
C2 - 18305138
AN - SCOPUS:44349152442
SN - 0964-6906
VL - 17
SP - 1695
EP - 1704
JO - Human molecular genetics
JF - Human molecular genetics
IS - 11
ER -