Association Study Of HNF1A In Women With Polycystic Ovary Syndrome

ObjectivePolycystic ovary syndrome(PCOS)is one of the most common female endocrinopathies and affects 5-8%of reproductive-aged women worldwide.PCOS is characterized by two of the following three criteria:clinical and/or biochemical androgen excess,oligo-ovulation and/or anovulation,and polycystic ovaries.In addition,women with PCOS often have an increased risk of suffering from metabolic syndrome,dyslipidemia,type 2 diabetes mellitus(T2DM)and cardiovascular disease.Currently,several susceptibility genes of these disorders have been proven to be related to PCOS,including THADA,TCF7L2,YAP1,and MTNRI B.The hepatocyte nuclear factor 1 alpha gene(HNF1A)is located on human chromosome 12q24 and contains 9 exons.HNF1A expression is enriched in the liver,and it is also expressed in many other tissues such as the pancreas,kidneys,ovaries,and testes.HNF1A encodes a transcription factor that belongs to the homeobox protein family,and HNF1A binds to the promoters of a variety of genes that are expressed predominantly in the liver.In addition,HNF1A is essential for the expression of several target genes(e.g.DYRK1B and SLC2A2)involved in lipoprotein metabolism and glucose-stimulated insulin secretion.Recently,it has been confirmed that defects in the HNF1A gene are a cause of maturity-onset diabetes of the young type 3 and are related to the development of T2DM.Furthermore,there is a study that has shown that HNF1A is a common susceptibility gene for several diseases,such as coronary artery disease(CAD),hypertension,and dyslipidemia and is associated with the concentration of C-reactive protein(CRP)in the plasma.All of these results suggest that the HNF1A gene might be involved in the etiology of PCOS.Previous studies have shown that rs2393791,located in intron 1 of HNF1A,is linked with changes in CRP and is involved in hypertension and hypertriglyceridemia.SNP rs7305618,which is located at the 5’ flank of HNF1A,has been shown to be associated with the risk of T2DM in a Chinese population.In another genome-wide association study,rs7305618 was found to be strongly associated with plasma CRP concentration.Therefore,to determine any correlation between the HNF1A gene and PCOS,we selected the above two SNPs(rs2393791 A/G and rs7305618 C/T)for analysis.Materials and Methods1138 PCOS and 1125 healthy control Han Chinese women were recruited from Reproductive Hospital Affiliated to Shandong University.Serum hormone,blood lipid level,and genomic DNA were obtained from the peripheral blood for this research.Two single-nucleotide polymorphisms(SNPs)-rs2393791 and rs7305618-located in HNF1A were genotyped using the Sequenom MassARRAY system.ResultsThe allele frequencies of SNP rs7305618 had significant differences between PCOS patients and controls after adjusting for age and BMI(p = 0.023).Besides,PCOS patients carrying the rs7305618 CC genotype shown a higher testosterone level than the patients with CT+TT genotypes after being adjusted by age and BMI(p= 0.019).Conclusion:A SNP located in the HNF1A gene is associated with PCOS among Han Chinese women.This suggested that variations in HNF1A might confer risk for PCOS.