TY - JOUR
T1 - A variant of the glucocorticoid receptor gene is not associated with adrenal androgen excess in women with polycystic ovary syndrome
AU - Kahsar-Miller, Melissa
AU - Azziz, Ricardo
AU - Feingold, Eleanor
AU - Witchel, Selma F.
N1 - Funding Information:
Supported in part by grants RO1-HD29364 (R.A.) and R29-HD34808 (S.F.W.) from the National Institutes of Health, Bethesda, Maryland and grants from the Pennsylvania Chapter of the American Heart Association (S.F.W.) and the Genentech Foundation (S.F.W.).
PY - 2000
Y1 - 2000
N2 - Objective: To determine whether the frequency of the N363S variant of the glucocorticoid receptor (GRL) was increased in women with PCOS and adrenal androgen (AA) excess. Design: Prospective case-control study. Setting: University reproductive endocrinology laboratory and outpatient clinic. 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 the N363S allele representing a variant of GRL. Result(s): Fifty-four PCOS patients with (DHEAS ≥ 3000 ng/mL) and 55 without (DHEAS ≤ 2,500 ng/mL) AA excess, respectively, were studied. Six of 109 (5.5%) patients studied were found to be heterozygous carriers of the A→G base pair substitution at cDNA position 1220, resulting in the missense mutation N363S. Of these six, four had excessive AA secretion (i.e., excess DHEAS levels). There was no significant difference in the allele frequency of the GRL variant between PCOS patients with and without AA excess and controls (3.7% [95% confidence interval: 1.0%-5.7%], 1.8% [0.2%-6.0%], and 3.3% [2.3%-6.0%]). None of the subjects were found to be homozygous for the N363S allele. Conclusion(s): The N363S variant of GRL was an uncommon occurrence in our population of healthy women and PCOS patients and did not appear to play a major role in the genetic predisposition to PCOS or to AA excess in PCOS. Copyright (C) 2000 American Society for Reproductive Medicine.
AB - Objective: To determine whether the frequency of the N363S variant of the glucocorticoid receptor (GRL) was increased in women with PCOS and adrenal androgen (AA) excess. Design: Prospective case-control study. Setting: University reproductive endocrinology laboratory and outpatient clinic. 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 the N363S allele representing a variant of GRL. Result(s): Fifty-four PCOS patients with (DHEAS ≥ 3000 ng/mL) and 55 without (DHEAS ≤ 2,500 ng/mL) AA excess, respectively, were studied. Six of 109 (5.5%) patients studied were found to be heterozygous carriers of the A→G base pair substitution at cDNA position 1220, resulting in the missense mutation N363S. Of these six, four had excessive AA secretion (i.e., excess DHEAS levels). There was no significant difference in the allele frequency of the GRL variant between PCOS patients with and without AA excess and controls (3.7% [95% confidence interval: 1.0%-5.7%], 1.8% [0.2%-6.0%], and 3.3% [2.3%-6.0%]). None of the subjects were found to be homozygous for the N363S allele. Conclusion(s): The N363S variant of GRL was an uncommon occurrence in our population of healthy women and PCOS patients and did not appear to play a major role in the genetic predisposition to PCOS or to AA excess in PCOS. Copyright (C) 2000 American Society for Reproductive Medicine.
KW - Adrenal
KW - Androgen
KW - Genetics
KW - Glucocorticoid receptor
KW - Hirsutism
KW - Polycystic ovary syndrome
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U2 - 10.1016/S0015-0282(00)01620-4
DO - 10.1016/S0015-0282(00)01620-4
M3 - Article
C2 - 11119758
AN - SCOPUS:0033636386
SN - 0015-0282
VL - 74
SP - 1237
EP - 1240
JO - Fertility and sterility
JF - Fertility and sterility
IS - 6
ER -