Variants in the CD36 gene locus determine whole-body adiposity, but have no independent effect on insulin sensitivity.
CD36 variants have been associated with type 2 diabetes, features of the metabolic syndrome, and alterations in lipid metabolism. In contrast, the effect of single-nucleotide polymorphisms (SNPs) in CD36 on insulin resistance is controversial in literature. Therefore, we investigated whether genetic variation within the CD36 gene locus affects insulin resistance in a well-phenotyped cohort of white European subjects at increased risk for type 2 diabetes. We genotyped 1,790 subjects (1,174 women, 616 men) for six SNPs tagging 100% of common variants (minor allele frequency ≥0.05) within the CD36 gene locus with an r² ≥ 0.8. All subjects underwent an oral glucose tolerance test (OGTT) and a subset additionally a hyperinsulinemic-euglycemic clamp (n = 523). Ectopic hepatic lipids (n = 346) were assessed by magnetic resonance spectroscopy. After appropriate adjustment and Bonferroni correction for multiple comparisons, the four CD36 SNPs rs9784998, rs3211883, rs3211908, and rs3211956 significantly associated with BMI and rs3211883 and rs3211908 significantly associated with waist circumference (all P < 0.0042). In contrast, CD36 SNPs rs3211816 and rs3211960 were not associated with measures of adiposity (all P ≥ 0.11). No reliable association was detected between the six CD36 SNPs and insulin sensitivity or ectopic hepatic lipid accumulation after adjustment for age, gender, and BMI. In the long run, genetic variation within the CD36 locus may contribute to metabolic disease via its effect on body adiposity, but not via an independent effect on insulin sensitivity.
Division of Endocrinology, Diabetology, Angiology, Nephrology, and Clinical Chemistry, Department of Internal Medicine, Eberhard Karls University Tübingen, Member of the German Center for Diabetes Research (DZD), Tübingen, Germany.
Martin
M
Heni
Karsten
K
Müssig
Fausto
F
Machicao
Jürgen
J
Machann
Fritz
F
Schick
Claus D
CD
Claussen
Norbert
N
Stefan
Andreas
A
Fritsche
Hans-Ulrich
HU
Häring
Harald
H
Staiger
D000273:Adipose Tissue; D050154:Adiposity / Q000235:genetics*; D000328:Adult; D018955:CD36 Antigens / Q000235:genetics*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D044465:White People / Q000235:genetics*
D018955:CD36 Antigens