CLINICAL STUDY Polymorphisms of TCF7L2 gene in South Brazilian women with polycystic ovary syndrome: a cross-sectional study Ramon Bossardi Ramos 1 , Denusa Wiltgen 1 and Poli Mara Spritzer 1,2 1 Gynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clı ´nicas de Porto Alegre, Rua Ramiro Barcelos, 2350, 90035-003 Porto Alegre, RS, Brazil and 2 Laboratoryof Molecular Endocrinology, Department of Physiology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil (Correspondence should be addressed to P M Spritzer at Gynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clı ´nicas de Porto Alegre; Email: spritzer@ufrgs.br) Abstract Objective: To assess whether TCF7L2 single nucleotide polymorphisms rs7903146 C/T and rs11196236 C/T are associated with polycystic ovary syndrome (PCOS) in South Brazilian women. Design: Cross-sectional study. Methods: Two hundred PCOS patients and 102 non-hirsute, ovulatory controls were genotyped by real-time PCR. Haplotypes were constructed from the combination of both polymorphisms. Frequencies were inferred using the PHASE 2.1.1 software. Results and conclusions: The distribution of rs7903146 (PCOS, 54.4% CC; 28.5% CT; 17.1% TT; controls, 51.0% CC; 37.0% CT; 12.0% TT) and rs11196236 (PCOS, 4.3% CC; 33.5% CT; 62.2% TT; controls, 3.2% CC; 35.5% CT; 61.3% TT) was similar between the groups. rs7903146 and rs11196236 were not in linkage disequilibrium (jD 0 jZ0.34; r 2 Z0.07). PCOS participants were younger, with higher age-adjusted BMI, waist circumference, blood pressure, triglycerides, insulin, homeostasis model assessment index to estimate insulin resistance and total testosterone, and lower HDL-C and sex hormone binding globulin vs controls. In PCOS, no differences between genotypes and haplotypes were found for clinical and metabolic variables. However, for each T (rs7903146) and T (rs11196236) allele added to the haplotypes, a variation of 5.87 cm in waist (P trendZ0.01), 10.7 mg/dl in total cholesterol (P trendZ0.03), and 10.3 mg/dl in LDL-C (P trendZ0.01) was recorded. TCF7L2 variants are probably not implicated in PCOS development in South Brazilian women. European Journal of Endocrinology 169 569–576 Introduction Polycystic ovary syndrome (PCOS) is a complex endocrine disease characterized by hyperandrogenism and chronic anovulation. It is associated with metabolic disturbances such as central obesity, insulin resistance, dyslipidemia, and increased risk of diabetes and hypertension (1, 2, 3, 4, 5, 6). Current evidence indicates that PCOS is a multi- factorial polygenic disorder, whose pathogenesis and clinical presentation are influenced by both genetic susceptibility and environmental exposure (5, 7). To date, a number of genes have been reported to be associated with PCOS. Most of them are presumed to be relevant to the pathogenesis of PCOS, such as the genes encoding steroid biosynthesis enzymes and androgen and insulin receptors. However, a variant contributing substantially to the development of PCOS has not been identified (8, 9). Recently, common variants of the transcription factor 7-like 2 (TCF7L2) gene on chromosome 10q25.2 have been found to contribute to the risk of type 2 diabetes (T2DM) in various ethnic groups (10, 11, 12, 13). Association studies on the single nucleotide polymorphisms (SNPs) of the TCF7L2 gene in PCOS women have produced controversial data, with some studies showing association between SNPs rs7903146 and rs11196236 with obesity-related traits (14) and peripheral insulin resistance (15) and others reporting no such association (16, 17). Therefore, the aim of our study was to assess whether TCF7L2 SNPs rs7903146 C/T and rs11196236 C/T or their haplotypes are associated with PCOS and to determine a possible impact of these polymorphisms on anthropometric and metabolic variables in PCOS women from Southern Brazil. Subjects and methods Patients We studied 302 women, including 200 PCOS patients and 102 non-hirsute women with regular ovulatory European Journal of Endocrinology (2013) 169 569–576 ISSN 0804-4643 q 2013 European Society of Endocrinology DOI: 10.1530/EJE-13-0105 Online version via www.eje-online.org Downloaded from Bioscientifica.com at 06/17/2020 10:21:28AM via free access