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.

Higher chylomicron remnants and LDL particle numbers associate with CD36 SNPs and DNA methylation sites that reduce CD36

“…The most significant promoter SNPs identified to influence CM levels and TG clearance (rs1931694, rs13228738, rs3211842) are in strong LD with variants previously associated with MetS or coronary artery disease (22,48,49). Similarly, the 3′UTR variant, rs7755, identified to associate with LDL and to trend with higher CM remnants has been CD36 transcriptional regulator (Fig.…”

“…Earlier genetic studies linked CD36 to fasting lipids (21, 48), MetS (22,(49)(50)(51), and stroke risk (44). However, information related to the role of the gene in postprandial lipid metabolism, which plays an important role in etiology of MetS and cardiovascular disease, remains limited.…”

“…In addition, CD36 functions in transducing cell type-specific intracellular signaling that serves to regulate lipid utilization (17)(18)(19) or the immune response (20). Variants in the CD36 gene have been shown to influence fasting lipids (21,22) and risk of metabolic syndrome (MetS) (22). Evidence from CD36-null mouse models and CD36-deficient humans suggests that the protein regulates postprandial TGs and cholesterol metabolism.…”

Recent fat intake modulates fat taste sensitivity in lean and overweight subjects

“…Allelic variation within the putative receptors that govern fatty acid taste (that is, within the genes that regulate GPR40, 120 and CD36) have already been established, [19][20][21] however, their association to taste remains unknown and these association will need to be investigated in subsequent studies. Interestingly, attenuated taste sensitivity to monosodium glutamate has recently been reported among OB women.…”

CD36-deficient congenic strains show improved glucose tolerance and distinct shifts in metabolic and transcriptomic profiles

“…Although rare, complete deficiencies of Cd36 were reported in humans (Yamamoto et al, 1994;Kashiwagi et al, 1996) and a murine model featuring complete knockout of Cd36 is available (Febbraio et al, 1999), models carrying the 'incomplete' type of mutation may relevantly represent the more subtle functional consequences of common polymorphisms in human Cd36 gene. Actually, several single-nucleotide polymorphisms in the human Cd36 gene were recently associated with lipid levels, metabolic syndrome (Love-Gregory et al, 2008;Noel et al, 2010) or obesity (Bokor et al, 2010), although the latter has not been unanimously confirmed (Choquet et al, 2010).…”