Association Study Of Polycystic Ovary Syndrome Associated With Genetic Polymorphisms Of Neurotrophins Signaling Pathway Genes In Guangxi Zhuang And Han People

Objectives The aim of this study is to estimate the association between geneticpolymorphisms of neurotrophins signaling pathway genes (AKT2、IRSI、FRS2、MAPK13、IRAK3、NTRK2、SHC4)and the susceptibility to Polycystic ovarysyndrome in Guangxi Zhuang and Han people, layed the foundation of thegenetic mechanisms of Polycystic ovary syndrome in Guangxi Zhuang peopleand Han people.Methods A case-control study was performed to study the genetics of polycysticovary syndrome (PCOS). The PCOS patients were diagnosed according to thecriterion of the Rotterdam conference of European society of humanreproduction and embryology and the American society for reproductivemedicin（eESHRE/ASRM）in2003. The subjects in the association analysis were564unrelated PCOS patients (258Zhuang and306Han) and550unrelatedhealthy controls (282Zhuang and268Han). A SNPscan genotyping method wascarried out to analysis7single nucleotide polymorphisms(SNPs)(AKT2genevariant rs2304186, IRSI gene variant rs3731590，FRS2gene variant rs3201， MAPK13gene variant rs2071864，IRAK3gene variant rs1152911, NTRK2genevariant rs1627784and SHC4gene variant rs9806753). Statistical analyses werecarried out with SPSS16.0for windows, SHEsis, GMDR0.9.Result1.The essential feature of research objectsThe age distribution of case and control of Zhuang、Han people andcombination population are statistically significant(P=0.000); Among theZhuang and Han people of case and control are not statisticallysignificant(P=0.153); The different genotypes of rs2071864variants Zhuang、Han people are statistically significant(P=0.034); The different genotypes ofother variants are not statistically significant(P>0.050).2. Hardy-weinberg equilibriumThe genotype distribution of controls of Zhuang、Han people conform tohardy-weinberg equilibrium (P>0.050).3. The results for the SNPs of neurotrophins signaling pathway genesassociated PCOS.（1）Zhuang peopleOne SNP were statistically significant associated with PCOS in Zhuangpeople. The SNP was FRS2gene variant rs3201(TTvs. CT, OR=0.663,95%CI=0.452-0.972, P=0.035; TTvs. CT+CC, OR=0.686,95%CI=0.477-0.986,P=0.042). However, other SNPs in neurotrophins signaling pathway were notstatistically significant associated with PCOS in Zhuang people (P>0.050).（2）Han peopleTwo SNPs were statistically significant associated with PCOS in Hanpeople. They were IRAK3gene variant rs1152911(Tvs. C：OR=0.739，95%CI=0.577-0.946，P=0.016；TTvs. CC：OR=0.531，95%CI=0.320-0.882， P=0.014；TT+CTvs. CC：OR=1.562，95%CI=1.004-2.430，P=0.048；TTvs.CT+CC：OR=0.681，95%CI=0.464-1.000，P=0.050)and NTRK2gene variantrs1627784（Tvs. C：OR=1.367，95%CI=1.039-1.800，P=0.026；TTvs. CT+CC：OR=1.462，95%CI=1.031-2.075，P=0.033).（3）The combination populationTwo SNPs were statistically significant associated with PCOS in thecombination population. They were IRAK3gene variant rs1152911(Tvs. C：OR=0.806，95%CI=0.675-0.963，P=0.018；TTvs. CC：OR=0.658，95%CI=0.462-0.938，P=0.021), NTRK2gene variant rs1627784(Tvs. C, OR=0.836,95%CI=0.705-0.992, P=0.040) and rs4680(AA+GAvs. GG, OR=0.785,95%CI=0.635-0.971, P=0.026), TH gene variant rs6356(Tvs. C：OR=1.261，95%CI=1.037-1.533，P=0.020；TTvs. CC：OR=1.638，95%CI=1.105-2.644，P=0.043；TTvs. CT+CC：OR=1.302，95%CI=1.014-1.672，P=0.039).4. The results of haplotype analysisFour haplotypes(Crs3201-Crs1152911,Crs3201-Trs1152911,Trs3201-Crs1152911andTrs3201-Trs1151911)which were inferenced from FRS2gene variant rs3201andIRAK2gene variant rs1152911, the results are as follows: Zhuang people: Allthe haplotypes were not statistically significant associated with PCOS in Zhuangsamples. Han people: The Trs3201-Trs1151911haplotype was statistically significantassociated with PCOS (OR=1.404，95%CI=1.107-1.781，P=0.005). However,other haplotypes were not statistically significant associated with Han PCOS.The combination population: The Crs3201-Crs1152911haplotype was statisticallysignificant associated with PCOS(OR=1.290，95%CI=1.000-1.662，P=0.049);The Trs3201-Trs1151911haplotype was statistically significant associated withPCOS(OR=0.789，95%CI=0.666-0.935，P=0.006). Other haplotypes were notstatistically significant associated with PCOS(P>0.050). 5.The results of gene-gene interaction analysisThe GMDR analysis suggested that no gene-gene interactions werestatistically significant associated with PCOS in Zhuang and Hanpeople(P>0.050). The seven sites gene-gene interaction of AKT2rs2304186、IRS1rs3731594、FRS2rs3201、MAPK13rs2071864、IRAK3rs1152911、SHC4rs9806753、NTRK2rs16277842might cooperatively contribute to PCOS incombination population. However, logistic regression models suggested that nogene-gene interactions were statistically significant associated with PCOS incombination population (P>0.050).Conclusion1.The FRSE2gene variant rs3201was associated with PCOS of Zhuang people；The IRAK3gene variant rs1152911and the NTRK2gene variant rs1627784wasassociated with the Han people PCOS. The NTRK2gene variant rs1627784wasassociated with the susceptibility of Han people PCOS. The IRAK3gene variantrs1152911and the NTRK2gene variant rs1627784was associated with thesusceptibility of combination population polycystic ovary syndrome.2.The Trs3201-Trs1151911haplotype from FRS2gene variant rs3201and IRAK2genevariant rs1152911may increase the risk of PCOS in Han people significantly.The Crs3201-Crs1152911haplotype may increase the risk of PCOS in combinationpopulation significantly. The Trs3201-Trs1151911haplotype may reduce the risk ofPCOS in combination population significantly.