Association Of Androgen And Glucocorticoid Metabolic Key Gene Polymorphisms With Genetic Susceptibility To Polycystic Ovary Syndrome

Objective:Hyperandrogenemia is one of the most important features of polycystic ovary syndrome (PCOS).17β-hydroxysteroid dehydrogenase type 5 (HSD17B5) and 17fi-hydroxysteroid dehydrogenase type 6 (HSD17B6) genes encoding special enzymes participating in androgen synthesis and metabolism. The current study was to evaluate the association between polymorphisms of the two genes and the risk of PCOS.Methods:In this study,335 patients with PCOS and 354 controls were recruited. The genotype distribution of HSD17B5 (rs1937845 and rsl2529) and HSD17B6 (rs898611) were detected using TaqMan method. The relationships between polymorphisms of the two genes and anthropometric, metabolic, hormonal and functional parameters of PCOS were explored. The allele frequency and genotype distribution of cases and controls were analyzed using Stata software.Results and conclusion:We found that CT genotype frequency and T allele frequency of rs1937845 in PCOS women were significantly higher than those in control. CT genotype and T allele of rs 1937845 were associated with an increased risk of PCOS significantly (P= 0.002, P= 0.012). In patients with PCOS, the polymorphisms of rs 12529 (G>C) and rs 1937845 (C>T) in HSD17B5 were strongly associated with the high level of testosterone. The TT-carriers of rs 1937845 had a significantly increased homeostatic model assessment-B% (HOMA-B%) (P= 0.045) and that might be associated with the high risk of insulin resistance. However, no significant difference was found in the genotype frequencies of the polymorphisms of rs12529 in HSD17B5 and rs898611 in HSD17B6 between PCOS patients and the control. The two polymorphisms of HSD17B5 are associated with hyperandrogenemia in Chinese PCOS patients. These results suggested that women carrying the CT genotype and T allele of rs1937845 had a high risk of PCOS. Further studies need to be done to confirm the role of the polymorphism in PCOS and investigate the mechanism involved with the two polymorphisms of HSD17B5 underlying hyperandrogenemia of PCOS.Objective:To evaluate whether single nucleotide polymorphisms of HSD11B1 (rs846908) and H6PD (rs6688832 and rs 17368528) are associated with polycystic ovary syndrome (PCOS) in Chinese population.Methods:A case-control study was implemented to investigate the relation between HSD11B1 and H6PD polymorphisms and PCOS. Patients with PCOS (n=335) and controls (n=354) were recruited in this study. Genetic variants of HSD11B1 (rs846908) and H6PD (rs6688832 and rs 17368528) were analyzed in both patients and controls by the TaqMan method.Results and conclusion:We found a statistical difference of the genotypic frequencies of the rs6688832 polymorphism of H6PD between PCOS and control women, with the GG genotype being more commonly found in controls than in patients with PCOS. We observed a significantly lower risk of G allele in rs6688832 in control group vs the patients with PCOS (P=0.040). After testing endocrine parameters, we found significant difference in the levels of follicle-stimulating hormones (FSH) in rs6688832 between AA and AG genotype. The AG carriers of polymorphism rs6688832 was strongly associated with lower level of FSH (P=0.039) and higher risk of hyperandrogenism (P=0.016) in patients with PCOS. When we divided subjects into different groups according to age and BM, we found the frequency of G allele in rs6688832 was significant higher in the controls than that in PCOS patients in the subgroup of BMI>23 (P=0.037). In conclusion, our findings showed a statistical association between H6PD rs6688832 and PCOS risk in Chinese population. The G allele of rs6688832 of H6PD might exert potential genetic protective role against the development of PCOS, especially in overweight women. PCOS patients with AG genotype in rs6688832 might confer risk to the phenotype of hyperandrogenemia of PCOS.