Polymorphisms in the SHBG gene influence serum SHBG levels in women with polycystic ovary syndrome

Edmond P. Wickham, Kathryn G. Ewens, Richard S. Legro, Andrea Dunaif, John E. Nestler, Jerome F. Strauss

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Context: Single-nucleotide polymorphisms (SNPs) in the SHBG gene are associated with type 2 diabetes mellitus. SHBG has also been proposed as a candidate gene for the polycystic ovary syndrome (PCOS). Objective: The study aims were 1) to determine whether any of four SHBG SNPs (rs1779941, rs6297, rs6259, and rs727428) are associated with PCOS and 2) to determine whether SNP genotype influences SHBG levels in PCOS women. Design: Using the transmission disequilibrium test, evidence of associations between SHBG SNPs and PCOS were analyzed. Additionally, correlations between SHBG levels and SNP genotype, body mass index, non-SHBG-bound testosterone, and insulin resistance estimated by the homeostasis model were determined. Setting: The study was conducted at academic medical centers. Patients or Other Participants: A total of 430 families having a proband with PCOS were included in the family-based study. Associations between SNP genotypes, SHBG, and metabolic parameters were determined in 758 women with PCOS including probands from the family cohort. Main Outcome Measures: Primary outcome measures included transmission frequency of SNP alleles and correlation coefficients between SHBG and allele frequency/metabolic parameters. Results: No evidence of association between SNPs of interest and PCOS was found. However, in multivariate analyses, SHBG levels varied significantly with rs1799941 and rs727428 genotype after controlling for body mass index, non-SHBG-bound testosterone, and homeostasis model for insulin resistance. Conclusions: Although SHBG SNPs associated with type 2 diabetes mellitus do not appear to be associated with PCOS status, rs1799941 and rs727428 genotypes are associated with SHBG levels independent of the effects of insulin resistance and obesity.

Original languageEnglish (US)
Pages (from-to)E719-E727
JournalJournal of Clinical Endocrinology and Metabolism
Volume96
Issue number4
DOIs
StatePublished - Apr 1 2011

Fingerprint

Polycystic Ovary Syndrome
Polymorphism
Single Nucleotide Polymorphism
Nucleotides
Genes
Serum
Genotype
Insulin Resistance
Insulin
Medical problems
Type 2 Diabetes Mellitus
Testosterone
Body Mass Index
Homeostasis
Outcome Assessment (Health Care)
Gene Frequency
Multivariate Analysis
Obesity
Alleles

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Wickham, Edmond P. ; Ewens, Kathryn G. ; Legro, Richard S. ; Dunaif, Andrea ; Nestler, John E. ; Strauss, Jerome F. / Polymorphisms in the SHBG gene influence serum SHBG levels in women with polycystic ovary syndrome. In: Journal of Clinical Endocrinology and Metabolism. 2011 ; Vol. 96, No. 4. pp. E719-E727.
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abstract = "Context: Single-nucleotide polymorphisms (SNPs) in the SHBG gene are associated with type 2 diabetes mellitus. SHBG has also been proposed as a candidate gene for the polycystic ovary syndrome (PCOS). Objective: The study aims were 1) to determine whether any of four SHBG SNPs (rs1779941, rs6297, rs6259, and rs727428) are associated with PCOS and 2) to determine whether SNP genotype influences SHBG levels in PCOS women. Design: Using the transmission disequilibrium test, evidence of associations between SHBG SNPs and PCOS were analyzed. Additionally, correlations between SHBG levels and SNP genotype, body mass index, non-SHBG-bound testosterone, and insulin resistance estimated by the homeostasis model were determined. Setting: The study was conducted at academic medical centers. Patients or Other Participants: A total of 430 families having a proband with PCOS were included in the family-based study. Associations between SNP genotypes, SHBG, and metabolic parameters were determined in 758 women with PCOS including probands from the family cohort. Main Outcome Measures: Primary outcome measures included transmission frequency of SNP alleles and correlation coefficients between SHBG and allele frequency/metabolic parameters. Results: No evidence of association between SNPs of interest and PCOS was found. However, in multivariate analyses, SHBG levels varied significantly with rs1799941 and rs727428 genotype after controlling for body mass index, non-SHBG-bound testosterone, and homeostasis model for insulin resistance. Conclusions: Although SHBG SNPs associated with type 2 diabetes mellitus do not appear to be associated with PCOS status, rs1799941 and rs727428 genotypes are associated with SHBG levels independent of the effects of insulin resistance and obesity.",
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Polymorphisms in the SHBG gene influence serum SHBG levels in women with polycystic ovary syndrome. / Wickham, Edmond P.; Ewens, Kathryn G.; Legro, Richard S.; Dunaif, Andrea; Nestler, John E.; Strauss, Jerome F.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 96, No. 4, 01.04.2011, p. E719-E727.

Research output: Contribution to journalArticle

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T1 - Polymorphisms in the SHBG gene influence serum SHBG levels in women with polycystic ovary syndrome

AU - Wickham, Edmond P.

AU - Ewens, Kathryn G.

AU - Legro, Richard S.

AU - Dunaif, Andrea

AU - Nestler, John E.

AU - Strauss, Jerome F.

PY - 2011/4/1

Y1 - 2011/4/1

N2 - Context: Single-nucleotide polymorphisms (SNPs) in the SHBG gene are associated with type 2 diabetes mellitus. SHBG has also been proposed as a candidate gene for the polycystic ovary syndrome (PCOS). Objective: The study aims were 1) to determine whether any of four SHBG SNPs (rs1779941, rs6297, rs6259, and rs727428) are associated with PCOS and 2) to determine whether SNP genotype influences SHBG levels in PCOS women. Design: Using the transmission disequilibrium test, evidence of associations between SHBG SNPs and PCOS were analyzed. Additionally, correlations between SHBG levels and SNP genotype, body mass index, non-SHBG-bound testosterone, and insulin resistance estimated by the homeostasis model were determined. Setting: The study was conducted at academic medical centers. Patients or Other Participants: A total of 430 families having a proband with PCOS were included in the family-based study. Associations between SNP genotypes, SHBG, and metabolic parameters were determined in 758 women with PCOS including probands from the family cohort. Main Outcome Measures: Primary outcome measures included transmission frequency of SNP alleles and correlation coefficients between SHBG and allele frequency/metabolic parameters. Results: No evidence of association between SNPs of interest and PCOS was found. However, in multivariate analyses, SHBG levels varied significantly with rs1799941 and rs727428 genotype after controlling for body mass index, non-SHBG-bound testosterone, and homeostasis model for insulin resistance. Conclusions: Although SHBG SNPs associated with type 2 diabetes mellitus do not appear to be associated with PCOS status, rs1799941 and rs727428 genotypes are associated with SHBG levels independent of the effects of insulin resistance and obesity.

AB - Context: Single-nucleotide polymorphisms (SNPs) in the SHBG gene are associated with type 2 diabetes mellitus. SHBG has also been proposed as a candidate gene for the polycystic ovary syndrome (PCOS). Objective: The study aims were 1) to determine whether any of four SHBG SNPs (rs1779941, rs6297, rs6259, and rs727428) are associated with PCOS and 2) to determine whether SNP genotype influences SHBG levels in PCOS women. Design: Using the transmission disequilibrium test, evidence of associations between SHBG SNPs and PCOS were analyzed. Additionally, correlations between SHBG levels and SNP genotype, body mass index, non-SHBG-bound testosterone, and insulin resistance estimated by the homeostasis model were determined. Setting: The study was conducted at academic medical centers. Patients or Other Participants: A total of 430 families having a proband with PCOS were included in the family-based study. Associations between SNP genotypes, SHBG, and metabolic parameters were determined in 758 women with PCOS including probands from the family cohort. Main Outcome Measures: Primary outcome measures included transmission frequency of SNP alleles and correlation coefficients between SHBG and allele frequency/metabolic parameters. Results: No evidence of association between SNPs of interest and PCOS was found. However, in multivariate analyses, SHBG levels varied significantly with rs1799941 and rs727428 genotype after controlling for body mass index, non-SHBG-bound testosterone, and homeostasis model for insulin resistance. Conclusions: Although SHBG SNPs associated with type 2 diabetes mellitus do not appear to be associated with PCOS status, rs1799941 and rs727428 genotypes are associated with SHBG levels independent of the effects of insulin resistance and obesity.

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