Hum. Reprod. Advance Access originally published online on July 21, 2005
Human Reproduction 2005 20(11):3184-3191; doi:10.1093/humrep/dei205
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Polymorphisms in the insulin receptor substrate-1 (IRS-1) gene and the insulin receptor substrate-2 (IRS-2) gene influence glucose homeostasis and body mass index in women with polycystic ovary syndrome and non-hyperandrogenic controls
Departments of 1 Endocrinology and 2 Molecular Genetics, Hospital Ramón y Cajal, Madrid, Spain
3 To whom correspondence should be addressed at: Department of Endocrinology, Hospital Ramón y Cajal, Carretera de Colmenar km 9'1, E-28034 Madrid, Spain. E-mail: hescobarm.hrc{at}salud.madrid.org
BACKGROUND: We aimed to evaluate the influence of the Gly972Arg variant of the insulin receptor substrate-1 gene (IRS-1) and the Gly1057Asp variant in IRS-2 on insulin resistance and glucose tolerance in women with polycystic ovary syndrome (PCOS) and healthy controls. METHODS: Genotypes, allelic frequencies, indexes of insulin resistance, glucose tolerance and hormone profiles were studied in a large sample of Spanish PCOS (n = 103) women compared with a control group (n = 48) of healthy women matched for body mass index. RESULTS: No differences in genotype or allelic frequencies were found between PCOS patients and healthy controls. When considering control subjects and PCOS patients as a whole, IRS-1 Arg972 carriers also presented with increased fasting insulin (133 ± 60 versus 95 ± 67 pmol/l, P = 0.008) and insulin resistance measured by homeostasis model assessment (4.3 ± 2.1 versus 3.1 ± 2.4, P = 0.009) compared with subjects homozygous for Gly972 alleles. These differences were even higher when restricting the analysis to PCOS patients. Subjects homozygous for the Gly1057 allele of IRS-2 presented with increased 60 and 90 min oral glucose tolerance test (OGTT) glucose levels compared with carriers of one or two Asp1057 alleles (7.9 ± 2.1 versus 7.1 ± 2.1 mmol/l, P = 0.042 and 7.0 ± 2.1 versus 6.0 ± 1.8 mmol/l, P = 0.014), and a similar tendency was observed for 120 min OGTT glucose levels. CONCLUSIONS: The Gly972Arg in IRS-1 and Gly1057Asp in IRS-2 polymorphisms influence glucose homeostasis in premenopausal women, but are not associated with PCOS.
Key words: insulin resistance/insulin-receptor substrate/polycystic ovary syndrome/polymorphisms
* These authors contributed equally to this work.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Simoni, C.B. Tempfer, B. Destenaves, and B.C.J.M. Fauser Functional genetic polymorphisms and female reproductive disorders: Part I: polycystic ovary syndrome and ovarian response Hum. Reprod. Update, September 1, 2008; 14(5): 459 - 484. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. San Millan, F. Alvarez-Blasco, M. Luque-Ramirez, J. I. Botella-Carretero, and H. F. Escobar-Morreale The PON1-108C/T polymorphism, and not the polycystic ovary syndrome, is an important determinant of reduced serum paraoxonase activity in premenopausal women Hum. Reprod., December 1, 2006; 21(12): 3157 - 3161. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Alvarez-Blasco, J. I. Botella-Carretero, J. L. San Millan, and H. F. Escobar-Morreale Prevalence and characteristics of the polycystic ovary syndrome in overweight and obese women. Arch Intern Med, October 23, 2006; 166(19): 2081 - 2086. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.F. Escobar-Morreale, G. Villuendas, J.I. Botella-Carretero, F. Alvarez-Blasco, R. Sanchon, M. Luque-Ramirez, and J.L. San Millan Adiponectin and resistin in PCOS: a clinical, biochemical and molecular genetic study Hum. Reprod., September 1, 2006; 21(9): 2257 - 2265. [Abstract] [Full Text] [PDF]
|
|