Insulin Gene Polymorphism in Women with Polycystic Ovary Syndrome

Abstract

Insulin resistance is one of the main characteristics of polycystic ovary syndrome (PCOS) and is probably genetically predisposed. Possible associations of variable nucleotide tandem repeat (VNTR) polymorphism of the insulin gene (INS) with insulin resistance and PCOS in Slovene patients were investigated. A total of 117 PCOS patients and 108 age-matched female controls were genotyped for the INS VNTR polymorphism using real-time polymerase chain reaction and measurement of appropriate biochemical and clinical parameters. Serum fasting insulin (I ₀) levels and the homeostasis model assessment index were significantly elevated in PCOS patients compared with controls. Class III INS VNTR alleles were significantly more frequent in the PCOS group. The interaction between body mass index and INS VNTR genotype was a significant predictor of serum I ₀ level. The interaction of obesity and the III/III INS VNTR genotype might be a risk factor for the development of PCOS.

Keywords

Insulin resistance Insulin gene Genetic polymorphism Obesity Polycystic ovary syndrome Genetic basis of human diseases

References

Atamer

Demir

Bayhan

: Serum levels of leptin and homocysteine in women with polycystic ovary syndrome and its relationship to endocrine, clinical and metabolic parameters. J Int Med Res 2008; 36: 96–105.

Goodarzi

Erickson

Port

: β-Cell function: A key pathological determinant in polycystic ovary syndrome. J Clin Endocrinol Metab 2005; 90: 310–315.

Franks

: Polycystic ovary syndrome. N Engl J Med 1995; 333: 853–861.

Legro

Strauss

: Molecular progress in infertility: Polycystic ovary syndrome. Fertil Steril 2002; 78: 569–576.

Waterworth

Bennett

Gharani

: Linkage and association of insulin gene VNTR regulatory polymorphism with polycystic ovary syndrome. Lancet 1997; 349: 986–990.

San Millan

Corton

Villuendas

: Association of the polycystic ovary syndrome with genomic variants related to insulin resistance, type 2 diabetes mellitus, and obesity. J Clin Endocrinol Metab 2004; 89: 2640–2646.

Kennedy

German

Rutter

: The minisatellite in the diabetes susceptibility locus IDDM2 regulates insulin transcription. Nat Genet 1995; 9: 293–298.

Vafiadis

Bennett

Colle

: Imprinted and genotype-specific expression of genes at the IDDM2 locus in pancreas and leucocytes. J Autoimmun 1996; 9: 397–403.

Bennett

Lucassen

Gough

: Susceptibility to human type 1 diabetes at IDDM2 is determined by tandem repeat variation at the insulin gene minisatellite locus. Nat Genet 1995; 9: 284–292.

10.

Bennett

Todd

: Human type 1 diabetes and the insulin gene: Principles of mapping polygenes. Annu Rev Genet 1996; 30: 343–370.

11.

Le Stunff

Fallin

Bougnères

: Paternal transmission of the very common class I INS VNTR alleles predisposes to childhood obesity. Nat Genet 2001; 29: 96–99.

12.

Dunger

Ong

Huxtable

: Association of the INS VNTR with size at birth. ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood. Nat Genet 1998; 19: 98–100.

13.

Urbanek

Legro

Driscoll

: Thirty-seven candidate genes for polycystic ovary syndrome: Strongest evidence for linkage is with follistatin. Proc Natl Acad Sci 1999; 96: 8573–8578.

14.

Vanková

Vrbíková

Hill

: Association of insulin gene VNTR polymorphism with polycystic ovary syndrome. Ann N Y Acad Sci 2002; 967: 558–565.

15.

Calvo

Telleria

Sancho

: Insulin gene variable number of tandem repeats regulatory polymorphism is not associated with hyperandrogenism in Spanish women. Fertil Steril 2002; 77: 666–668.

16.

Powell

Haddad

Bennett

: Analysis of multiple data sets reveals no association between the insulin gene variable number tandem repeat element and polycystic ovary syndrome or related traits. J Clin Endocrinol Metab 2005; 90: 2988–2993.

17.

Homburg

: What is polycystic ovarian syndrome? A proposal for a consensus on the definition and diagnosis of polycystic ovarian syndrome. Hum Reprod 2002; 17: 2495–2499.

18.

The Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group: Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 2004; 81: 19–25.

19.

Balen

Laven

Tan

: Ultrasound assessment of the polycystic ovary: International consensus definitions. Hum Reprod Update 2003; 9: 505–514.

20.

Balen

Conway

Homburg

(eds): Polycystic Ovary Syndrome: a Guide to Clinical Management; Defining the Polycystic Ovary Syndrome. Philadelphia: Taylor & Francis, 2005; pp 7–22.

21.

Handelsman

: Empirical estimation of free testosterone from testosterone and sex hormone-binding globulin immunoassays. Eur J Endocrinol 2005; 152: 471–478.

22.

Lucassen

Julier

Beressi

: Susceptibility to insulin dependent diabetes mellitus maps to a 4.1 kb segment of DNA spanning the insulin gene and associated VNTR. Nat Genet 1993; 4: 305–310.