Abstract
BackgroundInsulin resistance and glucose dysmetabolism in polycystic ovary syndrome (PCOS) are related with the polymorphisms in the genes encoding the insulin receptor substrate (IRS) proteins, especially Gly972Arg/Ala513Pro polymorphism being reported to be associated with type-2 diabetes and PCOS. We intended to assess the prevalence of abnormal glucose tolerance (AGT) and insulin resistance in Taiwanese PCOS women. We also tried to assess whether the particular identity of Gly972Arg/Ala513Pro polymorphic alleles of the IRS-1 gene mutation can be used as an appropriate diagnostic indicator for PCOS.MethodsWe designed a prospective clinical study. Forty-seven Taiwanese Hoklo and Hakka women, diagnosed with PCOS were enrolled in this study as were forty-five healthy Hoklo and Hakka women as the control group. Insulin resistance was evaluated with fasting insulin, fasting glucose/insulin ratio, and homeostasis model assessment index for insulin resistance (HOMAIR). The genomic DNA of the subjects was amplified by PCR and digested by restriction fragmented length polymorphism (RFLP) with Bst N1 used for codon 972 and Dra III for codon 513.ResultsAGT was found in 46.8% of these PCOS patients and was significantly related to high insulin resistance rather than the low insulin resistance. Those patients with either insulin resistance or AGT comprised the majority of PCOS affected patients (AGT + fasting insulin ≥17: 83%, AGT + glucose/insulin ratio ≥6.5: 85.1%, AGT + HOMAIR ≥ 2: 87.2%, and AGT + HOMAIR ≥ 3.8: 72.3%). None of the tested samples revealed any polymorphism due to the absence of any Dra III recognition site or any Bst N1 recognition site in the amplified PCR fragment digested by restriction fragmented length polymorphism.ConclusionThere is significantly high prevalence of AGT and insulin resistance in PCOS women, but Gly972Arg and Ala513Pro polymorphic alleles of IRS-1 are rare and are not associated with the elevated risk of PCOS amongst Taiwanese subjects. This is quite different from the similar study in phylogenetically diverged Caucasian subjects.
Highlights
Insulin resistance and glucose dysmetabolism in polycystic ovary syndrome (PCOS) are related with the polymorphisms in the genes encoding the insulin receptor substrate (IRS) proteins, especially Gly972Arg/ Ala513Pro polymorphism being reported to be associated with type-2 diabetes and PCOS
The biokinetic response of IRS-1 and IRS-2 to tyrosine protein kinases depends upon the binding specificity and affinity of the tyrosine phosphorylation sites within the IRS, which can be altered by mutated aminoacid polymorphisms within the phosphotyrosine-binding (PTB) domain [7]
Independently of whether patients featured non-insulin dependent diabetes mellitus (NIDDM) or not, the results revealed no evidence of any polymorphism in the regions encoding codon 972 of the IRS-1 for the Taiwanese population, 36.2% of our PCOS subjects revealed abnormal glucose tolerance (AGT) and 72.3–87.2% revealed either insulin resistance or AGT with respect to different criteria of insulin resistance
Summary
Insulin resistance and glucose dysmetabolism in polycystic ovary syndrome (PCOS) are related with the polymorphisms in the genes encoding the insulin receptor substrate (IRS) proteins, especially Gly972Arg/ Ala513Pro polymorphism being reported to be associated with type-2 diabetes and PCOS. The biokinetic response of IRS-1 and IRS-2 to tyrosine protein kinases depends upon the binding specificity and affinity of the tyrosine phosphorylation sites within the IRS, which can be altered by mutated aminoacid polymorphisms within the phosphotyrosine-binding (PTB) domain [7]. The Ser892Gly and Thr608Arg polymorphisms for non-insulin dependent diabetes mellitus (NIDDM) patients were reported, such a mutation revealing a consequent decrease in insulin-induced phosphorylation and PI 3-kinase activity [10,11]
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