The Correlation Research On The Polymorphism Of Androgen Receptor Gene In Women With Polycystic Ovary Syndrome

Objective:To investigate the role of the androgen receptor gene CAG repeat polymorphism on the formation of polycystic ovary syndrome (PCOS)and its association with hyperandrogenemia and hyperinsulinemia.Method:97 patients were recruited (2008 December to 2009 August)from the gynecological endocrine outpatient clinic who diagnosed as PCOS as case group,60 healthy volunteers were recruited as control group.All the subjects were excluded from other endocrinopathy and did not have any hormonal therapy for the past 3 months before the study. For the PCOS patients, circulating hormonal parameters and insulin releasing test were measured; Serum total T and fasting blood glucose and insulin were carried in control groups.The PCOS patients were divided into hyperandrogen-ic and normal-androgenic subgroups(Ⅰgroup andⅡgroup) according to Serum total androgen level,insulin resistance and non-insulin resistance subgroups(A group and B group)according to HOMA-IR. DNA was extracted from solidified blood clot of PCOS patients and control subjects, then genomic DNA was used for PCR amplification of the androgen receptor gene CAG microsatellite fragment. Agarose gel and denaturing polyacrylamide gel respectively detected the products, at last, sequencing of the DNA to determine the CAG repeat numbers.Results:1.The clinical and biochemical characteristics of the women with PCOS:1.1 The clinical characteristics of the women with PCOS:the mean age was 25.19±4.87 years,BMI was 26.85±4.56kg/m2;Among 97 patients 60.82% displayed obesity; Hyperandrogenism was 60.82% while 61.86% had insulin resistant. The overall incidence of abnormal glucose metabolism rate was 27.84%,in which 4.12%, IGT,17.53% and 6.19% displayed IFG,IGT and DM2,respectively; Moreover, two adolescents had abnormal glucose metabolism;71.13%patients manifested Oligomenorrhea,18.56%patients showed secondary amenorrhea and others displayed menorrhagia or bradymenorrhea; The incidence of acne, hirsutism were 40.2%,19.59%;72.16% cases were bilateral or unilateral polycystic ovarian changes and 16.49%patients with two ovaries enlarged,the rest had no obvious abnormalities.1.2 BMI, T, FPG, FINS,HOMA, HBCI were higher in PCOS group than control group, while ISI was lower, the difference were significant, consistent with the clinical features of PCOS.1.3 Serum sex hormones and glucose metabolic features in different groups1.3.1 According to the androgen level:HOMA-IR,HBCI,IAUC,FINS were higher inⅠgroup thanⅡgroup, while ISI was lower (P<0.05),The rest parameters had no significant difference.1.3.2 According to the HOMA-IR:T,HBCI,IAUC,FPG, FINS were higher in A group than B group,while ISI was lower (P<0.05);LH, LH/FSH is lower in A group than B group,although there is no significant difference.2.The study on the AR(CAG)n repeats and polycystic ovary syndrome2.1 The overall distribution of the AR-CAG:The AR-CAG repeat length ranged from 15 to 32 in PCOS patients majoring in 22,23 and from 16 to 29 in control subjects majoring in 22,24,20, most is 22 repeats in two groups and the mean CAG repeat length was similar in both groups.The median CAG repeat length for all alleles was 23,so The patients were divided into two groups:short group(≤23) and long(>23), based on the cut-off at 23 repeats.The short group distributed in PCOS group and control group were 69.07% and 60.00% respectively, while long group were 30.93% and 40.00%, it was similar in both groups.2.2 The association of AR(CAG)n repeats and hyperandrogenism:The AR-CAG repeats was higher inⅠgroup thanⅡgroup, although the difference was no statistically significant; Correlation test in the PCOS patients showed a significant positive correlation between the CAG repeats and the T level.According the CAG repeats, the short group contained inⅠandⅡgroup were 62.71 and 78.95%,respectively, while long group were 37.29% and 21.05%,short group inⅠgroup was lower thanⅡgroup, while long group inⅠgroup was higher thanⅡgroup,but it was no significant difference(P=0.09).In PCOS patients with acne or hirsutism, had a lower number of CAG repeats compared with PCOS patients without acne and without hirsutism.The subgroup of PCOS patients with the combination of short repeat and elevated T level had the highest percentage(62.16%) of cases with acne or hirsutism and the subgroup of PCOS patients with the combination of a long repeat and non-elevated T level had the lowest percentage (37.50%).2.3 The association of AR(CAG)n repeats and hyperinsulinism:No difference in the mean AR-CAG repeat lengths A of and B subgroups of PCOS patients was found; Moreover according the CAG repeats, the short group contained in A and B group were 39.34% and 47.22%,respectively, while long group were 60.66% and 52.78%, it was was similar in both groups.Conclusion:1.PCOS patients had the endocrinology and metabolism characteristic of obesity, hyperandrogenism, insulin resistance. The effect of hyperandrogenism and hyperinsulinism may appear to be additive. The prevalence of abnormal glucose metabolic was higher than normal people, and may be younger than expected.2.There is androgen receptor CAG microsatellite polymorphism in PCOS patients and control group,the CAGn repeat length polymorphism may not be a major determinant of PCOS,but women with a shorter repeat may sensitivly develop to PCOS.3.There was a significant positive correlation between the CAG repeats and the T level.Higher androgen levels and shorter CAG repeats may together influence the hyperandrogenic phenotype of the PCOS.This may be one of the reseasons of the difference phenotype of PCOS.4. There was no correlation between the CAG repeats and hyperinsulinism, may be indirectly affected hyperinsulinism though hyperandrogenism.