SNP analysis of follistatin gene associated with polycystic ovarian syndrome

Palanisamy Panneerselvam¹, Kanakarajan Sivakumari¹, Ponmani Jayaprakash¹, Ramanathan Srikanth^2
1Department of Zoology, Presidency College, Chennai, Tamil Nadu, India; ²Department of Biotechnology, Sri Venkateswara College of Engineering, Chennai, Tamil Nadu, India

Abstract: Follistatin has been reported as a candidate gene for polycystic ovarian syndrome (PCOS) based on linkage and association studies. In this study, investigation of polymorphisms in the FST gene was done to determine if genetic variation is associated with susceptibility to PCOS. The nucleotide sequence of human follistatin and the protein sequence of human follistatin were retrieved from the NCBI database using Entrez. The follistatin protein of human was retrieved from the Swiss-Prot database. There are 344 amino acids and the molecular weight is 38,007 Da. The ProtParam analysis shows that the isoelectric point is 5.53 and the aliphatic index is 61.25. The hydropathicity is -0.490. The domains in FST protein are as follows: Pfam-B 5005 domain from 1 to 92; EGF-like subdomain from 93 to 116; Kazal 1 domain, occurred in three places, namely, 118–164, 192–239, and 270–316. There are 31 single-nucleotide polymorphisms (SNPs) for this gene. Some are nonsynonymous, some occur in the intron region, and some in an untranslated region. Two nonsynonymous SNPs, namely, rs11745088 and rs1127760, were taken for analysis. In the SNP rs11745088, the change is E152Q. Likewise, in rs1127760, the change is C239S. SIFT (Sorting Intolerant from Tolerant) showed positions of amino acids and the single letter code of amino acids that can be tolerated or deleterious for each position. There were six SNP results and each result had links to it. The dbSNP id, primary database id, and the type of mutation whether silent and if occurring in coding region are given as phenotype alterations. The FASTA format of protein was given to the nsSNP Analyzer tool, and the variation E152Q and C239S were given as inputs in the SNP data field. E152Q change was neutral and C239S causes disease. Using PANTHER for evolutionary analysis of coding SNPs, the protein sequence was given as input and analyzed for the E152Q and C239S SNPs for deleterious effect on protein function. The genetic association database results showed that FST gene SNPs are linked to PCOS coming under the disease class of metabolic disorders. The list of intronic and synonymous SNPs, with their nucleotide position, amino acid change information, and dbSNP link, is provided for further analysis.

Keywords: FST, polycystic ovarian syndrome, single-nucleotide polymorphism analysis