RESUMEN
Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder with high prevalence in women around the world. The identification of single-nucleotide polymorphisms (SNPs) through genome-wide association studies has classified it as a polygenic disease. Most studies have independently evaluated the contribution of each SNP to the risk of PCOS. Few studies have assessed the effect of epistasis among the identified SNPs. Therefore, this exploratory study aimed to evaluate the interaction of 27 SNPs identified as risk candidates and their contribution to the pathogenesis of PCOS. The study population included 49 control women and 49 women with PCOS with a normal BMI. Genotyping was carried out through the MassARRAY iPLEX single-nucleotide polymorphism typing platform. Using the multifactor dimensionality reduction (MDR) method, the interaction between SNPs was evaluated. The analysis showed that the best interaction model (p < 0.0001) was composed of three loci (rs11692782-FSHR, rs2268361-FSHR, and rs4784165-TOX3). Furthermore, a tendency towards synergy was evident between rs2268361 and the SNPs rs7371084-rs11692782-rs4784165, as well as a redundancy in rs7371084-rs11692782-rs4784165. This pilot study suggests that epistasis may influence PCOS pathophysiology. Large-scale analysis is needed to deepen our understanding of its impact on this complex syndrome affecting thousands of women.
Asunto(s)
Epistasis Genética , Predisposición Genética a la Enfermedad , Síndrome del Ovario Poliquístico , Polimorfismo de Nucleótido Simple , Humanos , Síndrome del Ovario Poliquístico/genética , Femenino , Adulto , Colombia/epidemiología , Estudio de Asociación del Genoma Completo , Estudios de Casos y Controles , Genotipo , Adulto JovenRESUMEN
Polycystic ovary syndrome (PCOS) is a multifactorial and polygenic endocrine-metabolic disorder in women of reproductive age. SNPs in the THADA gene have been identified as PCOS risk loci. In this study, we evaluated the frequency of five polymorphisms in a sample of Colombian women with PCOS, and their association with clinical and endocrine-metabolic parameters. Forty-nine women with PCOS and forty-nine healthy women were included. Allelic discrimination was performed in the THADA gene by iPLEX and the MassARRAY system (Agena Bioscience). Haploview software was conducted to analyze the linkage disequilibrium (LD) and haplotypes of polymorphisms. There was an association between the genotypes TT of rs12468394, CC + AA of rs12468394, and GG of rs6544661 and an increase in the levels of free testosterone. The CC + AA of rs12468394 genotype also was associated with an increase of androstenedione levels. THADA gene SNPs were not associated with PCOS risk. There was very strong LD among the SNPs. No significant differences in the frequency of haplotypes between groups were observed. The statistical power of this analysis is low because of the small number of samples analyzed. Additional studies involving large populations of Colombian women with PCOS are needed to verify the role of the THADA gene in this disorder.
RESUMEN
Polycystic ovary syndrome (PCOS) is one of the most common endocrine-metabolic disorders in women of reproductive age. It is characterized by an increase in the biosynthesis of androgens, anovulation, and infertility. PCOS has been reported as a polygenic entity in which multiple single nucleotide polymorphisms (SNPs) are associated with the clinical features of the pathology. Herein, we describe the common polymorphic variants in genes related to PCOS, their role in its pathogenesis, and etiology. Whole-genome association studies have been focused on women from Asian and European populations. The most common genes associated with PCOS are DENND1A, THADA, FSHR, and LHCGR. However, other genes have been associated with PCOS such as AMH, AMHR2, ADIPOQ, FTO, HNF1A, CYP19, YAP1, HMGA2, RAB5B, SUOX, INSR, and TOX3. Nevertheless, the relationship between the biological functions of these genes and the development of the pathology is unclear. Studies in each gene in different populations do not always comply with a general pattern, so researching these variants is essential for better understanding of this polygenic syndrome. Future population studies should be carried out to evaluate biological processes, incidence rates, allelic and genotypic frequencies, and genetic susceptibility factors that predispose PCOS.