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Horm Metab Res 2010; 42(8): 575-584
DOI: 10.1055/s-0030-1249020
Humans, Clinical

© Georg Thieme Verlag KG Stuttgart · New York

Very High Frequency of the Polymorphism for the Insulin Receptor Substrate 1 (IRS-1) at Codon 972 (Glycine972Arginine) in Southern Italian Women with Polycystic Ovary Syndrome

M. A. Pappalardo1 , G. T. Russo2 , A. Pedone1 , A. Pizzo3 , I. Borrielli3 , G. Stabile1 , A. C. Artenisio1 , A. Amato4 , M. Calvani4 , D. Cucinotta2 , F. Trimarchi1 , S. Benvenga1 , 5 , 6
  • 1Sezione di Endocrinologia, Dipartimento Clinico Sperimentale di Medicina e Farmacologia, Università di Messina, Messina, Italy
  • 2Dipartimento di Medicina Interna, Università di Messina, Messina, Italy
  • 3Dipartimento di Scienze Ostetriche e Ginecologiche, Università di Messina, Messina, Italy
  • 4Sigma-Tau SpA, Pomezia, Italy
  • 5Master Childhood, Adolescent and Women's Endocrine Health, University of Messina, Messina, Italy
  • 6Programma di Endocrinologia Molecolare Clinica, AOU Policlinico G. Martino, Messina, Messina, Italy
Further Information

Publication History

received 17.09.2009

accepted 03.02.2010

Publication Date:
12 March 2010 (online)

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Abstract

A major component of the polycystic ovary syndrome (PCOS) is the insulin resistance. Only a few studies have evaluated the IRS-1 polymorphism at codon 972, sometimes in the absence of a control group, and with great variability in frequency (0–23% in PCOS vs. 0–17% in controls), and with no unequivocal relationships between the polymorphism and clinical or biochemical indexes. The aim of the work was to evaluate the frequency of the IRS-1 polymorphism at codon 972 in PCOS, and correlate it to clinical and biochemical indexes. We assessed the rs 1801278 polymorphic variant in the IRS-1 gene (Gly972Gly=wild-type; Gly972Arg=heterozygosity; Arg972Arg=homozygosity) in genomic DNA by restriction fragment length polymorphism. The study was conducted at an academic medical center with the participation of 65 women with PCOS and 27 age-matched healthy women (controls). Compared to controls, Gly972Arg was very frequent in PCOS (77% vs. 18%, p<0.0001); one PCOS woman was homozygous. Compared to wild-type PCOS, heterozygous PCOS women had only three significantly different indexes: higher fasting insulin, insulin resistance index, and lower 120 min OGTT glucose. Moreover, in the correlation analysis between any two clinical or biochemical variables, the Pearson's correlation coefficients were frequently of different magnitude in heterozygous PCOS versus wild-type PCOS. Overall, heterozygous PCOS had a greater number of statistically significant relationships between different clinical, metabolic and hormonal indexes: 44 direct and 9 inverse versus 6 and 3, respectively. The IRS-1 Gly972Arg has the highest frequency reported world-wide for PCOS women. This variant is associated with insulin resistance and higher fasting insulin in PCOS women.

Key words

insulin resistance - hyperandrogenism - single nucleotide polymorphisms

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Correspondence

M. A. PappalardoMD 

Unit of Endocrinology

Policlinico Universitario

“G. Martino”

Via Consolare Valeria

98125 Messina

Italy

Phone: +39/090/221 71 07

Fax: +39/090/221 35 18

Email: mapp20@libero.it

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