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.
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.
Villuendas
Gemma
G
Department of Endocrinology, Hospital Ramón y Cajal, Madrid, Spain.
Botella-Carretero
José I
JI
Roldán
Belén
B
Sancho
José
J
Escobar-Morreale
Héctor F
HF
San Millán
José L
JL
D000328:Adult; D019943:Amino Acid Substitution; D015992:Body Mass Index; D005260:Female; D005787:Gene Frequency; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis / Q000235:genetics*; D006801:Humans; D017588:Hyperandrogenism / Q000503:physiopathology; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D009765:Obesity / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics*; D011085:Polycystic Ovary Syndrome / Q000235:genetics* / Q000503:physiopathology*; D011110:Polymorphism, Genetic; D011972:Receptor, Insulin; D013030:Spain; D044465:White People / Q000235:genetics
C526292:IRS1 protein, human; C526297:IRS2 protein, human; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D011972:Receptor, Insulin; D005947:Glucose