CYR61 polymorphisms are associated with plasma HDL-cholesterol levels in obese individuals.
We have recently characterized the transcriptome of the omental adipose tissue of non-diabetic, obese men with and without the metabolic syndrome (MS). The cysteine-rich protein 61 (CYR61) is one of the most differentially expressed genes between the groups and has been selected for a detailed molecular investigation. Direct sequencing of complete CYR61 gene revealed five polymorphisms with minor allele frequency >5% in the promoter region (rs 3753794, rs 3753793 and rs 2297140), intron 1 (rs 2297141) and intron 2 (IVS 2+50). Chi-square test and logistic regression were applied to test for association between CYR61 polymorphisms and the individual MS components in a cohort of 697 obese individuals. In men and women, rs 3753794 and rs 3753793 (r2 = 0.77) were associated plasma HDL-cholesterol levels (p = 0.016 and p = 0.008). Carriers of the A allele for rs 3753794 were more likely to have high plasma HDL-cholesterol levels (1.50-fold; p = 0.016), as compared with G/G homozygotes and the A/A homozygotes for rs 3753793 were more likely to exhibit low plasma HDL-cholesterol levels (1.56-fold; p = 0.008), as compared with C/C homozygotes. Furthermore, an association between IVS 2+50 polymorphism and HDL-cholesterol was found in women and in men analyzed separately (p = 0.002 and p = 0.038, respectively). These results suggest that CYR61 is a promising candidate gene for lipoprotein/lipid perturbations.
Bouchard
L
L
Lipid Research Center, Nutraceuticals and Functional Foods Institute, and Department of Food Science and Nutrition, Laval University, Québec, Canada.
Tchernof
A
A
Deshaies
Y
Y
Lebel
S
S
Hould
F-S
FS
Marceau
P
P
Vohl
M-C
MC
D000328:Adult; D008076:Cholesterol, HDL / Q000097:blood*; D055515:Cysteine-Rich Protein 61; D005260:Female; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000235:genetics*; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000235:genetics; D020641:Polymorphism, Single Nucleotide
C501848:CCN1 protein, human; D008076:Cholesterol, HDL; D055515:Cysteine-Rich Protein 61; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins