Association of the T45G polymorphism in exon 2 of the adiponectin gene with polycystic ovary syndrome: role of Delta4-androstenedione

Background: Insulin resistance is a prominent feature of polycystic ovary syndrome (PCOS), independent of obesity. It is possible that insulin resistance in PCOS is genetically determined. Adiponectin is a protein that modulates insulin action and is regarded as a possible link between adiposity and insulin resistance. The objective of this study was to examine the role of the adiponectin gene T45G polymorphism, located in exon 2, in PCOS, since this polymorphism has been shown to be associated with obesity and insulin resistance.

Subjects and methods: Two hundred and thirty-two women were studied, and were classified as follows: 132 women with PCOS [62 with body mass index (BMI) > 25 kg/m2 and 70 with BMI < 25 kg/m2] and 100 ovulating women without hyperandrogenemia (controls: 19 with BMI > 25 kg/m2 and 81 with BMI < 25 kg/m2). From all subjects a whole-blood sample was taken and was used for isolation of peripheral blood leukocytes. The adiponectin T45G polymorphism, located in exon 2, was genotyped by amplification of genomic DNA. In all subjects, serum gonadotropin, androgen, 17-OH-progesterone, fasting glucose, insulin and adiponectin levels were measured between the third and sixth day of the menstrual cycle.

Results: A statistically significant difference was observed in the frequency of GG and TG genotypes between women with PCOS (40/132; 30.3%) and controls (19/100; 19.0%). In a subgroup of PCOS women with high Delta4-androstenedione levels (Delta4A > 3.11 ng/ml), a statistically significant difference between the frequencies of the genotypes was also noticed compared with the control group, in contrast to the subgroup with relatively low Delta4-androstenedione levels (Delta4A < 3.11 ng/ml). No significant associations were found between this adiponectin polymorphism and BMI, testosterone level, adiponectin levels and glucose-to-insulin ratio.

Conclusions: Our study suggests that adiponectin polymorphisms are not causatively involved in the metabolic disturbances of PCOS, but that an interaction between adiponectin and steroid synthesis or action might exist.