Abnormal glucose tolerance and insulin resistance in polycystic ovary syndrome amongst the Taiwanese population- not correlated with insulin receptor substrate-1 Gly972Arg/Ala513Pro polymorphism.
BACKGROUND
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. 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.


METHODS
We 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.


RESULTS
AGT 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 > or =17: 83%, AGT + glucose/insulin ratio > or =6.5: 85.1%, AGT + HOMAIR > or = 2: 87.2%, and AGT + HOMAIR > or = 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.


CONCLUSIONS
There 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.
Lin
Ta-Chin
TC
Department of Gynecology, Obstetrics, and Infertility, Kuo General Hospital, No, 22, Section 2, Ming-Sheng Road, Tainan, 70054, Taiwan. tachin@ksts.seed.net.tw
Yen
Jui-Mei
JM
Gong
Kum-Bing
KB
Kuo
Tsung-Cheng
TC
Ku
Dong-Chi
DC
Liang
Shu-Fen
SF
Wu
Ming-Jiuan
MJ
D000293:Adolescent; D000328:Adult; D000409:Alanine / Q000235:genetics; D019943:Amino Acid Substitution; D001120:Arginine / Q000235:genetics; D003920:Diabetes Mellitus / Q000175:diagnosis; D005260:Female; D018149:Glucose Intolerance / Q000175:diagnosis; D044882:Glucose Metabolism Disorders / Q000175:diagnosis*; D005951:Glucose Tolerance Test; D005998:Glycine / Q000235:genetics; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance; D010750:Phosphoproteins / Q000235:genetics*; D011085:Polycystic Ovary Syndrome / Q000175:diagnosis* / Q000208:ethnology; D020641:Polymorphism, Single Nucleotide; D011392:Proline / Q000235:genetics; D011446:Prospective Studies; D013624:Taiwan / Q000208:ethnology
C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D010750:Phosphoproteins; D001120:Arginine; D011392:Proline; D000409:Alanine; D005998:Glycine