CDKN2A-CDKN2B and IGF2BP2 gene polymorphisms in women with polycystic ovary syndrome

Insulin resistance is a core feature of PCOS. Genome-wide association studies (GWAS) have reported a number of SNPs with reproducible associations and susceptibilities to type 2 diabetes. We examined the potential association between the diabetogenic genes - CDKN2A-CDKN2B and IGF2BP2 - uncovered. Case-control study. Measurements: DNA samples from 552 PCOS patients and 559 age-matched controls were genotyped. Four SNPs (rs564398, rs1333040, rs10757278 and rs10811661) in CDKN2A-CDKN2B and one SNP (rs4402960) in IGF2BP2 were evaluated. To investigate the association between the presence of PCOS and each individual SNP, logistic regression analyses were performed using the homozygote of wild-type allele as the reference category. Compared with the 559 controls, we found that PCOS was significantly associated with heterozygote of the rs10757278 in CDKN2A-CDKN2B, and their ORs ranged from 1.10 to 1.89. None of the remaining four SNPs (rs564398, rs1333040, rs10757278, rs10811661 and rs4402960) were associated with PCOS. For further analysis, the PCOS patients were divided into two or three subgroups according to genotype, and the associations between the genotypes and insulin resistance or insulin secretory capacity were assessed. No SNPs were significantly associated with HOMA-IR, HOMA βcell (%), or 2-hour 75-g OGTT insulin levels in the PCOS patients; there were no significant associations with other serum hormonal and metabolic markers, such as androgen or glucose levels. Our results suggest that except rs10757278 in CDKN2A-CDKN2B, most of the CDKN2A-CDKN2B and IGF2BP2 polymorphisms are not associated with PCOS.