Genetic variants of cyclin-dependent kinase 5 regulatory subunit associated protein 1-like 1 and transcription factor 7-like 2 are not associated with polycystic ovary syndrome in Chinese women

Abstract

Polycystic ovary syndrome (PCOS) is a common disorder in women that shares many genetic features with type 2 diabetes mellitus. Novel risk loci for type 2 diabetes, single nucleotide polymorphism (SNP) rs7756992 in cyclin-dependent kinase 5 (CDK5) regulatory subunit associated protein 1-like 1 (CDKAL1), rs290487 and rs11196218 in transcription factor 7-like 2 (TCF7L2), were recently identified. The aim of this study was to test whether these loci are also associated with PCOS. We recruited 826 patients with PCOS and 620 healthy controls for case-control analysis. The genotypes of these three SNPs were identified. The relationships between PCOS-related clinical endocrine and metabolic features and genotypes were also analyzed. Genotype distribution of these three loci in case and control groups showed no deviation from the Hardy-Weinberg equilibrium. No significant differences in genotype and allele frequencies were found between patients with PCOS and healthy controls. No associations were observed between genotypes of the three SNPs and the clinical endocrine and metabolic features of patients with PCOS in case group after adjustment for body mass index. We concluded that rs7756992 in CDKAL1, rs290487 and rs11196218 in TCF7L2 have no associations with PCOS or PCOS-related clinical features.

Genetic determinants of polycystic ovary syndrome: progress and future directions

“…Another plausible candidate gene, the type 2 diabetes locus with the greatest odds for diabetes, TCF7L2 (39), has also been widely investigated in PCOS. Index SNPs associated with type 2 diabetes (rs7903146 and rs12255372) were not associated with PCOS (40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50), which was confirmed in meta-analyses of these individual studies (51,52). These findings are in contrast with the results of a third meta-analysis, which reported a significant association between rs7903146 and PCOS in European and Asian PCOS subjects, but not in African PCOS subjects (53).…”

Metabolic and cardiovascular genes in polycystic ovary syndrome: A candidate-wide association study (CWAS)

“…Regarding FTO (fat mass and obesity associated) genetic variants that affect diabetes risk via body mass index (BMI), the balance of the evidence in PCOS found association with BMI, fat mass or fat distribution and other metabolic traits and rarely reproductive hormones, with some studies also describing association with PCOS; some but not all of these associations lost significance after BMI adjustment [28,30–35]. Other diabetes loci found not to have any association with PCOS or its component traits include KCNJ11 (potassium inwardly rectifying channel, subfamily J, member 11) [26,36], CDKAL1 (CDK5 regulatory subunit-associated protein 1 like 1) [27], and SLC30A8 (solute carrier 30 (zinc transporter) member 8) [37]. The diabetogenic variant in the HHEX / IDE (hematopoietically expressed homeobox/insulin-degrading enzyme) region was not associated with PCOS [29]; however, a different SNP in IDE was associated with PCOS and insulin levels [38].…”

Genetics of the polycystic ovary syndrome

“…A recent study by Ewens et al also evaluated the association with the same two SNPs and PCOS using 400 probands and affected sisters, as well as 395 PCOS patients and 171 controls of European descent, and failed to detect significant associations with PCOS or β-cell function (measured by HOMA-IR and HOMA-%β) [62]. Likewise, two studies conducted in Asian populations to date have failed to provide any evidence of association between variants in TCF7L2 with PCOS [63,64]. …”