POLYMORPHISM OF GLYCOGEN-SYNTHETASE GENE IN POLYCYSTIC-OVARY-SYNDROME

OBJECTIVE Polycystic ovary syndrome is a heterogeneous disorder associ ated with a moderate degree of insulin resistance and a higher risk of developing NIDDM. The exact mechanism of insulin resistance is unclea r. This study examines the frequency of an Xbal polymorphism of the gl ycogen synthetase gene (A2 allele) as a marker of insulin resistance a nd seeks to relate the presence of the A2 allele to indices of insulin sensitivity in women with polycystic ovary syndrome (PCOS). METHODS I nsulin sensitivity was assessed by fasting insulin measurements, as we ll as following oral glucose tolerance test. An i.v. insulin tolerance test was performed to measure the rate of endogenous blood glucose di sposal following an i.v. bolus of insulin. Restriction fragment length polymorphism was performed with Xbal digestion of PCR amplified produ ct to detect the presence of Al and A2 allele. PATIENTS Seventy-one ob ese (BMI>25.1) and 19 nonobese (BMI<25) women with PCOS, and 62 contro ls (33 obese and 29 non-obese) participated in the study. RESULTS Obes e PCOS had significantly higher fasting insulin (P = 0.002) compared t o obese controls. There was no difference between non-obese PCOS and c ontrols. Twenty per cent of obese PCOS had impaired glucose tolerance. The A1A2 genotype was detected in 16 of the 150 (10.7%) subjects exam ined. Of these, 11/88 (12.5%) were PCOS and 5/62 (8%) were controls. T he A2A2 genotype was not present in any of the subjects. The A1A2 geno type was not detected in any of the subjects with impaired glucose tol erance. There was no significant difference in the incidence of the A1 A2 genotype between PCOS and controls or between the individual groups . There was no association between the presence of the A1A2 genotype a nd indices of insulin sensitivity. CONCLUSION The Xbal polymorphism (A 2 allele) of the glycogen synthetase gene was not over represented in the PCOS subject and did not relate to the indices of insulin sensitiv ity or glucose intolerance.