Prevalence of CYP21 mutations and IRS1 variant among women with polycystic ovary syndrome and adrenal androgen excess

Selma F. Witchel, Melissa Kahsar-Miller, Christopher E. Aston, Carlie White, Ricardo Azziz

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Objective: To determine whether frequencies of the mutations in the 21-hydroxylase (CYP21) gene and the G972R variant of the insulin receptor substrate-1 (IRS1) gene are increased in women with polycystic ovary syndrome (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 = 95). Intervention(s): Blood and DNA sampling before hormonal therapy. Main Outcome Measure(s): Polycystic ovary syndrome patient and healthy control genotypes, with the CYP21 and IRS1 variants. Result(s): Fifty-four PCOS patients with (DHEAS >3000 ng/mL) and 55 without (DHEAS <2500 ng/mL) AA excess, respectively, were studied. Of 109 patients studied, 16 (14.7%) were found to be heterozygous carriers of mutations in the CYP21 gene. Of these 16, 10 (62.5%) had excessive AA secretion (i.e., excess DHEAS levels). Fifteen patients (13.8%) were found to be heterozygous carriers of the IRS1 variant; 9 (60.0%) of these 15 had excessive AA secretion. There were no significant differences in the allele frequency of CYP21 mutations or the IRS1 variant between PCOS patients with and without AA excess, and controls. None of the subjects were found to be homozygous carriers of CYP21 mutations or the IRS1 variant. Combined heterozygosity for CYP21 mutations and the IRS1 variant was limited to women with PCOS and excessive AA (n = 3). Conclusion(s): The G972R variant of the IRS1 gene might represent a modifier locus among women who are heterozygous carriers of CYP21 mutations, potentially increasing their risk of developing AA excess in PCOS. Nonetheless, this IRS1 variant and CYP21 mutations seem to play a limited role in the development of PCOS in the population studied.

Original languageEnglish (US)
Pages (from-to)371-375
Number of pages5
JournalFertility and Sterility
Volume83
Issue number2
DOIs
StatePublished - Jan 1 2005

Fingerprint

Insulin Receptor Substrate Proteins
Polycystic Ovary Syndrome
Androgens
Mutation
Genes
Steroid 21-Hydroxylase
Endocrinology
Mutation Rate
Ambulatory Care Facilities
Gene Frequency
Case-Control Studies
Genotype
Outcome Assessment (Health Care)
DNA

Keywords

  • Adrenal
  • Androgen
  • CYP21
  • Genetics
  • Insulin receptor substrate-1
  • Polycystic ovary syndrome

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

Cite this

Prevalence of CYP21 mutations and IRS1 variant among women with polycystic ovary syndrome and adrenal androgen excess. / Witchel, Selma F.; Kahsar-Miller, Melissa; Aston, Christopher E.; White, Carlie; Azziz, Ricardo.

In: Fertility and Sterility, Vol. 83, No. 2, 01.01.2005, p. 371-375.

Research output: Contribution to journalArticle

Witchel, Selma F. ; Kahsar-Miller, Melissa ; Aston, Christopher E. ; White, Carlie ; Azziz, Ricardo. / Prevalence of CYP21 mutations and IRS1 variant among women with polycystic ovary syndrome and adrenal androgen excess. In: Fertility and Sterility. 2005 ; Vol. 83, No. 2. pp. 371-375.
@article{9ce527af962b4bdab7b49815195c378f,
title = "Prevalence of CYP21 mutations and IRS1 variant among women with polycystic ovary syndrome and adrenal androgen excess",
abstract = "Objective: To determine whether frequencies of the mutations in the 21-hydroxylase (CYP21) gene and the G972R variant of the insulin receptor substrate-1 (IRS1) gene are increased in women with polycystic ovary syndrome (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 = 95). Intervention(s): Blood and DNA sampling before hormonal therapy. Main Outcome Measure(s): Polycystic ovary syndrome patient and healthy control genotypes, with the CYP21 and IRS1 variants. Result(s): Fifty-four PCOS patients with (DHEAS >3000 ng/mL) and 55 without (DHEAS <2500 ng/mL) AA excess, respectively, were studied. Of 109 patients studied, 16 (14.7{\%}) were found to be heterozygous carriers of mutations in the CYP21 gene. Of these 16, 10 (62.5{\%}) had excessive AA secretion (i.e., excess DHEAS levels). Fifteen patients (13.8{\%}) were found to be heterozygous carriers of the IRS1 variant; 9 (60.0{\%}) of these 15 had excessive AA secretion. There were no significant differences in the allele frequency of CYP21 mutations or the IRS1 variant between PCOS patients with and without AA excess, and controls. None of the subjects were found to be homozygous carriers of CYP21 mutations or the IRS1 variant. Combined heterozygosity for CYP21 mutations and the IRS1 variant was limited to women with PCOS and excessive AA (n = 3). Conclusion(s): The G972R variant of the IRS1 gene might represent a modifier locus among women who are heterozygous carriers of CYP21 mutations, potentially increasing their risk of developing AA excess in PCOS. Nonetheless, this IRS1 variant and CYP21 mutations seem to play a limited role in the development of PCOS in the population studied.",
keywords = "Adrenal, Androgen, CYP21, Genetics, Insulin receptor substrate-1, Polycystic ovary syndrome",
author = "Witchel, {Selma F.} and Melissa Kahsar-Miller and Aston, {Christopher E.} and Carlie White and Ricardo Azziz",
year = "2005",
month = "1",
day = "1",
doi = "10.1016/j.fertnstert.2004.10.027",
language = "English (US)",
volume = "83",
pages = "371--375",
journal = "Fertility and Sterility",
issn = "0015-0282",
publisher = "Elsevier Inc.",
number = "2",

}

TY - JOUR

T1 - Prevalence of CYP21 mutations and IRS1 variant among women with polycystic ovary syndrome and adrenal androgen excess

AU - Witchel, Selma F.

AU - Kahsar-Miller, Melissa

AU - Aston, Christopher E.

AU - White, Carlie

AU - Azziz, Ricardo

PY - 2005/1/1

Y1 - 2005/1/1

N2 - Objective: To determine whether frequencies of the mutations in the 21-hydroxylase (CYP21) gene and the G972R variant of the insulin receptor substrate-1 (IRS1) gene are increased in women with polycystic ovary syndrome (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 = 95). Intervention(s): Blood and DNA sampling before hormonal therapy. Main Outcome Measure(s): Polycystic ovary syndrome patient and healthy control genotypes, with the CYP21 and IRS1 variants. Result(s): Fifty-four PCOS patients with (DHEAS >3000 ng/mL) and 55 without (DHEAS <2500 ng/mL) AA excess, respectively, were studied. Of 109 patients studied, 16 (14.7%) were found to be heterozygous carriers of mutations in the CYP21 gene. Of these 16, 10 (62.5%) had excessive AA secretion (i.e., excess DHEAS levels). Fifteen patients (13.8%) were found to be heterozygous carriers of the IRS1 variant; 9 (60.0%) of these 15 had excessive AA secretion. There were no significant differences in the allele frequency of CYP21 mutations or the IRS1 variant between PCOS patients with and without AA excess, and controls. None of the subjects were found to be homozygous carriers of CYP21 mutations or the IRS1 variant. Combined heterozygosity for CYP21 mutations and the IRS1 variant was limited to women with PCOS and excessive AA (n = 3). Conclusion(s): The G972R variant of the IRS1 gene might represent a modifier locus among women who are heterozygous carriers of CYP21 mutations, potentially increasing their risk of developing AA excess in PCOS. Nonetheless, this IRS1 variant and CYP21 mutations seem to play a limited role in the development of PCOS in the population studied.

AB - Objective: To determine whether frequencies of the mutations in the 21-hydroxylase (CYP21) gene and the G972R variant of the insulin receptor substrate-1 (IRS1) gene are increased in women with polycystic ovary syndrome (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 = 95). Intervention(s): Blood and DNA sampling before hormonal therapy. Main Outcome Measure(s): Polycystic ovary syndrome patient and healthy control genotypes, with the CYP21 and IRS1 variants. Result(s): Fifty-four PCOS patients with (DHEAS >3000 ng/mL) and 55 without (DHEAS <2500 ng/mL) AA excess, respectively, were studied. Of 109 patients studied, 16 (14.7%) were found to be heterozygous carriers of mutations in the CYP21 gene. Of these 16, 10 (62.5%) had excessive AA secretion (i.e., excess DHEAS levels). Fifteen patients (13.8%) were found to be heterozygous carriers of the IRS1 variant; 9 (60.0%) of these 15 had excessive AA secretion. There were no significant differences in the allele frequency of CYP21 mutations or the IRS1 variant between PCOS patients with and without AA excess, and controls. None of the subjects were found to be homozygous carriers of CYP21 mutations or the IRS1 variant. Combined heterozygosity for CYP21 mutations and the IRS1 variant was limited to women with PCOS and excessive AA (n = 3). Conclusion(s): The G972R variant of the IRS1 gene might represent a modifier locus among women who are heterozygous carriers of CYP21 mutations, potentially increasing their risk of developing AA excess in PCOS. Nonetheless, this IRS1 variant and CYP21 mutations seem to play a limited role in the development of PCOS in the population studied.

KW - Adrenal

KW - Androgen

KW - CYP21

KW - Genetics

KW - Insulin receptor substrate-1

KW - Polycystic ovary syndrome

UR - http://www.scopus.com/inward/record.url?scp=13544272786&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=13544272786&partnerID=8YFLogxK

U2 - 10.1016/j.fertnstert.2004.10.027

DO - 10.1016/j.fertnstert.2004.10.027

M3 - Article

VL - 83

SP - 371

EP - 375

JO - Fertility and Sterility

JF - Fertility and Sterility

SN - 0015-0282

IS - 2

ER -