Family Association Study Between Polymorphisms Of GGT1 Gene,HNF1A Gene And PCOS In Han Chinese

Background:Polycystic ovary syndrome (PCOS) is a very common endocrine-metabolic disorder. The syndrome is often associated with hyperinsulinemia, insulin resistance, type 2 diabetes,obesity, and cardiovascular diseases. Previous studies have observed that PCOS is a polygene inheritance disease and has strong familial clustering, suggesting that PCOS may be a genetic disease. The enzyme encoded by GGT1 gene is a type â…  gamma-glutamyltransferase that catalyzes the transfer of the glutamyl moiety of glutathione to a variety of amino acids and dipeptide acceptors. Some studies show that GGT1 is associated with cardiovascular disease and metabolic syndrome. The protein encoded by HNF1A gene is a transcription factor required for the expression of several liver-specific genes. Defects in this gene are a cause of maturity onset diabetes of the young type 3 (MODY3) and also can result in the appearance of hepatic adenomas. Because that PCOS is characterized by its association with endocrine-metabolic disorders like obesity, type â…¡ diabetes and atherosclerosis, we speculate GGT1 gene and HNF1A gene may be associated with PCOS. Family-based analysis was performed using the transmission disequilibrium test(TDT)to assess the association between single nucleotide polymorphisms(SNPs)in the GGT1 gene, HNF1A gene and PCOS. This method is not influenced by population stratification or genetic heterogeneity and environmental contributions.Methods:A total of 310 family trios were recruited and performed a family-based analysis to assess linkage and association between single nucleotide polymorphism(SNP) (rs4820599) of GGT1 gene,SNPs (rs7305618 and rs2393791) of HNF1A gene and PCOS.Results:1)The three SNPs were in Hardy-Weinberg equilibrium (P>0.05);2)Using the transmission disequilibrium test (TDT), we failed to find that rs4820599 (p=0.302), rs7305618 (p=0.908) and rs2393791 (p=0.861) were significantly overtransmitted to PCOS offspring from their parents.Conclusion:No significant evidence of association or linkage was found in the three tested markers, indicating that our family samples did not support susceptibility of the GGT1 gene and HNF1A gene to PCOS.