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SNP analysis of follistatin gene associated with polycystic ovarian syndrome.

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.

SUBMITTER: Panneerselvam P

PROVIDER: S-EPMC3170008 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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SNP analysis of follistatin gene associated with polycystic ovarian syndrome.

Panneerselvam Palanisamy P Sivakumari Kanakarajan K Jayaprakash Ponmani P Srikanth Ramanathan R

Advances and applications in bioinformatics and chemistry : AABC 20101213

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. T ...[more]

PMID: 21918632

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Project description:Is there a relationship between the genetic risk for polycystic ovary syndrome (PCOS) and genetic variants that influence timing of menopause?The genetic risk score, which sums the contribution of variants at all menopause loci, was associated with PCOS.Ovarian parameters and anti-Mullerian hormone levels suggest that women with PCOS should have a later age at menopause.The study was a case-control examination of genetic variants associated with age at menopause in a discovery cohort of women with PCOS (n = 485) and controls (n = 407) from Boston recruited from 2003 to 2012. Replication was performed in women from Greece (cases, n = 884 and controls, n = 311).PCOS was defined by the National Institutes of Health criteria in Boston and Greece (n = 783), with additional subjects fulfilling the Rotterdam criteria (hyperandrogenism, polycystic ovary morphology and regular menses) in Greece (n = 101). Controls in Boston and Greece had regular menstrual cycles and no hyperandrogenism. Allele frequencies for variants previously associated with age at menopause were examined in PCOS cases and controls, along with the relationship to quantitative traits.The variant rs11668344-G was associated with decreased risk of PCOS (odds ratio: 0.77 [0.59-0.93]; P = 0.004). There was a strong relationship between the late menopause allele rs12294104-T and increased LH levels (? ± SE; 0.26 ± 0.06; P = 5.2 × 10(-5)) and the LH:FSH ratio (0.28 ± 0.06; P = 2.7 × 10(-6)). The minor allele at rs10852344-T was associated with smaller ovarian volume (-0.16 ± 0.05; P = 0.0012). A genetic risk score calculated from 16 independent variants associated with age at menopause was also associated with PCOS (P < 0.02), LH and the LH:FSH ratio (both P < 0.05).The variant rs11668344 was not associated with PCOS in the Greek cohort, but results exhibited the same direction of effect as the Boston cohort. However, it is possible that the individual association was a false positive in the Boston cohort.The study demonstrates that gene variants known to influence age at menopause are also associated with risk for PCOS. Further, our data suggest that the relationship between age at menopause and PCOS may be explained, at least in part, by effects on LH levels and follicle number. The data point to opposing influences of the genetic variants on both menopausal age and PCOS.The project was supported by award number R01HD065029 from the Eunice Kennedy Shriver National Institute of Child Health & Human Development, award number 1 UL1 RR025758, Harvard Clinical and Translational Science Center, from the National Center for Research Resources and award 1-10-CT-57 from the American Diabetes Association. C.K.W. is a consultant for Takeda Pharmaceuticals.NCT00166569.

Project description:IntroductionPolycystic ovary syndrome (PCOS) is caused by the hormonal environment in utero, abnormal metabolism, and genetics, and it is common in women of childbearing age. A large number of studies have reported that lncRNA is important to the biological process of cancer and can be used as a potential prognostic biomarker. Thus, we studied lncRNAs' roles in PCOS in this article.MethodsWe obtained mRNAs', miRNAs', and lncRNAs' expression profiles in PCOS specimens and normal specimens from the National Biotechnology Information Gene Expression Comprehensive Center database. The EdgeR software package is used to distinguish the differentially expressed lncRNAs, miRNAs, and mRNAs. Functional enrichment analysis was carried out by the clusterProfiler R Package, and the lncRNA-miRNA-mRNA interaction ceRNA network was built in Cytoscape plug-in BiNGO and Database for Annotation, Visualization, and Integration Discovery (DAVID), respectively.ResultsWe distinguished differentially expressed RNAs, including 1087 lncRNAs, 14 miRNAs, and 566 mRNAs in PCOS. Among them, 410 lncRNAs, 11 miRNAs, and 185 mRNAs were contained in the ceRNA regulatory network. The outcomes from Gene Ontology (GO) analysis showed that the differentially expressed mRNAs (DEMs) were mainly enriched in response to the maternal process involved in female pregnancy, morphogenesis of embryonic epithelium, and the intracellular steroid hormone receptor signaling pathway. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis data showed that DEMs were primarily enriched in pathways related to the TGF-β signaling pathway, Type I diabetes mellitus, and glycolysis/gluconeogenesis. In addition, we chose NONHSAT123397, ENST00000564619, and NONHSAT077997 as key lncRNAs due to their high bearing on PCOS.ConclusionceRNA networks play an important role in PCOS. The research indicated that specific lncRNAs were related to PCOS development. NONHSAT123397, ENST00000564619, and NONHSAT077997 could be regarded as potential diagnostic mechanisms and biomarkers for PCOS. This discovery might provide more effective and more novel insights into the mechanisms of PCOS worthy of further exploration.

Project description:Polycystic ovarian syndrome (PCOS) is a kind of common gynecological endocrine disorder. And the mutations of melatonin receptor (MTNR) genes are related to the occurrence of PCOS. But previous researches have shown opposite results. So, the object of our systematic review and meta-analysis is to investigate the relationship between MTNR 1A/B polymorphisms and PCOS. PubMed, Embase, Ovid, the Cochrane Library, Web of Science and three Chinese databases (VIP, CNKI and Wanfang) were used to retrieve eligible articles published between January 1980 and February 2020. And we used the odds ratio (OR) and its 95% confidence interval (CI) to investigate the strength of the association by six genetic models, allelic, codominant (homozygous and heterozygous), dominant, recessive and superdominant models. Review Manager 5.3, IBM SPSS statistics 25 and Stata MP 16.0 software were used to do this meta-analysis. Our meta-analysis involved 2553 PCOS patients and 3152 controls, for two single nucleotide polymorphisms (rs10830963 C> G in MTNR1B and rs2119882 T> C in MTNR1A) and significant associations were found in some genetic models of these single nucleotide polymorphisms (SNPs). For rs10830963, strongly significant was found in the heterozygote model (GC vs. CC, P=0.02). Additionally, a slight trend was detected in the allelic (G vs. C), homozygote (GG vs. CC) and dominant (GG+GC vs. CC) model of rs10830963 (P=0.05). And after further sensitivity analysis, a study with high heterogeneity was removed. In the allelic (P=0.000), homozygote (P=0.001), dominant (P=0.000) and recessive (GG vs. GC+CC, P=0.001) model, strong associations between rs10830963 and PCOS were found. Moreover, for rs2119882, five genetic models, allelic (C vs. T, P=0.000), codominant (the homozygote (CC vs. TT, P=0.000) and heterozygote model (CT vs. TT, P=0.02), dominant (CC + CT vs. TT, P=0.03) and recessive model (CC vs. CT + TT, P=0.000) showed significant statistical associations with PCOS. MTNR1B rs10830963 and MTNR1B rs2119882 polymorphisms are associated with PCOS risk. However, the above conclusions still require being confirmed by much larger multi-ethnic studies.

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SNP analysis of follistatin gene associated with polycystic ovarian syndrome.

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SNP analysis of follistatin gene associated with polycystic ovarian syndrome.

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