A variant of the glucocorticoid receptor gene is not associated with adrenal androgen excess in women with polycystic ovary syndrome

Objective: To determine whether the frequency of the N363S variant of the g lucocorticoid receptor (GRL) was increased in women with PCOS and adrenal a ndrogen (AA) excess. Design: Prospective case-control study. Setting: University reproductive endocrinology laboratory and outpatient cl inic. Patient(s): Consecutive patients of non-Hispanic white race diagnosed with PCOS (n = 114) and healthy controls (n = 92). Intervention(s): Blood and DNA sampling before hormonal therapy. Main Outcome Measure(s): PCOS patient and healthy control genotypes, with t he N363S allele representing a variant of GRL. Result(s): Fifty-four PCOS patients with (DHEAS greater than or equal to 30 00 ng/mL) and 55 without (DHEAS less than or equal to 2,500 ng/mL) AA exces s, respectively, were studied. Six of 109 (5.5%) patients studied were foun d to be heterozygous carriers of the A-->G base pair substitution at cDNA p osition 1220, resulting in the missense mutation N363S. Of these six, four had excessive AA secretion (i.e., excess DHEAS levels). There was no signif icant difference in the allele frequency of the GRL variant between PCOS pa tients with and without AA excess and controls (3.7% [95% confidence interv al: 1.0%-5.7%], 1.8% [0.2%-6.0%], and 3.3% [2.3%-6.0%]). None of subjects w ere found to be homozygous for the N363S allele. Conclusion(s): The N363S variant of GRL was an uncommon occurrence in our p opulation of healthy women and PCOS patients and did not appear to play a m ajor role in the genetic predisposition to PCOS or to AA excess in PCOS. (F ertil Steril(R) 2000;74:1237-40. (C) 2000 by American Society for Reproduct ive Medicine).