Investigating pathogenic SNPs in androgen receptor with direct influence on polycystic ovary syndrome (PCOS) in women

Abstract

Abstract Background Polycystic ovary syndrome (PCOS) became one of the main reasons for infertility in women. It has an obvious effect on phenotype represented by hirsutism, increased body mass index, obesity, and acne, while biochemical tests show adverse hormonal imbalance with hyperandrogenism as testosterone levels increases. From molecular level point of view, pathogenic SNPs may change CAG repeats number along androgen receptor (AR) resulting in altered function of the gene causing different affinity to androgen hormones. Methods Recruiting 150 patients diagnosed with PCOS for the study, genomic DNA was extracted and amplified using specifically designed exon 1 PCR primers employing gene walking technique. The resulting amplicons were sequenced and thoroughly analyzed for polymorphism and CAG repeats number. Results Data obtained from recruiting 150 patients diagnosed with PCOS showed that sequences X:67545209–67545742; X:67545503–67545739 of exon 1 harbored 7 SNPs altered secondary structure of the resulting protein and forced toward the use of CAA as synonymous codon instead of the normal CAGs stretches. This led to produced alternative mRNA that eventually changed nonsense-mediated mRNA decay mechanism. Conclusion Probability of PCOS in women with polymorphic AR gene is higher than others, especially women with high number of CAG stretches. The new finding and highlight of this study is that alternative codon usage (CAAs) to produce the same amino acid (Gln) and compensate the reduced number of CAG repeats number may be attributed to epigenetic mechanism to mitigate the adverse effect of such change and maintain a normal function of AR gene. This finding was not previously reported in former studies.