Association of rs1342945 and rs12478601 single nucleotide polymorphisms with Polycystic Ovarian Syndrome (PCOS): a case control study and in silico analysis

Introduction & Objectives: Polycystic ovary syndrome (PCOS) is among the most general endocrine disorders of women, affecting near 5–15% of reproductive age women. The etiology of PCOS remains unknown; although, heritability studies proposed that there is a strong genetic susceptibility to the disorder. A previously presented genome-wide association study (GWAS) of PCOS found that several loci certify evidence. The aim of this study was to investigate the association of two single nucleotide polymorphisms (SNPs) in a case control study of women with PCOS referred to Jahad Daneshgahi infertility treatment center, Qom branch (ACECR).Materials & Methods: For this purpose, two polymorphisms in the THADA gene, which are called SNP (rs)12478601 and rs13429458, were selected from the data obtained by the International haplotype map (HapMap) Project regarding Chinese Han population, and were evaluated by tetra‑primer ARMS‑PCR. To explore possible relationships between SNP and phenotypic variation, different computational tools like SNP Nexus, UTRscan, Human Splicing Finder (HSF), Repeat Masker and RNAsnp Web Server PupaSuite were used for prioritization of high-risk SNP in (interionic and exotics 5’ and 3’-untranslated region (UTR) SNPs). Results: In this study for the first time it was shown that rs13429458 polymorphism is not associated with PCOS risk in Iranian women. On the other hand, data analysis indicated that the rs12478601 genotype significantly increased the risk of PCOS (p≤0.05). Also, prediction analysis of intronic SNP using the human splice finder web tool indicated that rs12478601 induces the abrogation or creation of such binding sites. In silico prediction indicated that it may has an impact on the RNA secondary structure and it located adjacent the signal sequence for poly adenylation. UTRscan demonstrated that this region is located upstream of open reading frame (uORF).Conclusion: Because several studies about PCOS are based on Han ethnic women, studies on women of other ethnic backgrounds and geographical origins are required. Repetition is necessary to determine whether the same variants conferring risk for PCOS in women all around the world. Bioinformatics analysis indicated that rs12478601 in intron may affect cryptic splice site. The molecular basis for SNP in splicing efficiency is largely unknown, but identification of the responsible factors could facilitate the development of therapies.

کلیدواژه ها:

PCOs ، SNP ، ARMS‑PCR ، Bioinformatics ، splice site