Study On The Association Of SNPs Of Rs10965235 And Rs2235529 With The Risk Of Ovarian Endometriosis

Objective: Endometriosis(EMs)is a common gynecological condition with complex etiology defined by the presence of endometrial glands and stroma outside the womb.Endometriosis is a common cause of both cyclic and chronic pelvic pain,reduced fertility,and reduced quality-of-life.The treatment is ineffective and prone to relapse.Ovarian endometriosis is the most typical lesions of the EMs.At present,the EMs etiology and pathogenesis is still unclear," theory of ectopic endometrium grow"," body cavity metaplasia theories "," theory of induction "," hereditary susceptibility " and " immune and inflammatory factor " are the main doctrine of endometriosis.As genetics and epidemiology research,more and more evidence that the EMs has a genetic predisposition.Genome-wide association study(GWAS)is the rise genetic research methods in recent years.Meta-analyses were conducted on four GWASs and four replication studies,showed that six out of nine SNPs remained genome-wide significant in other country.The experiment is to explore the association between rs10965235C/A and the rs2235529G/A polymorphisms loci with the incidence of ectopic endometriosis risk.Our study takes the lead in investigating the relationship between the above two in women from the North of China.Methods:This case-control study consisted of 580 surgically confirmed endometriosis cases and 606 healthy women as control.Five milliliters of venous peripheral blood was drawn from each subject into vacutainer tubes containing EDTA and stored at 4 ? less than one week.At the same time recorded the history and personal and family information.After sampling,the genomic DNA was extracted within one week using proteinase-K digestion followed by a salting out procedure.The rs10965235C/A and rs2235529G/A polymorphisms were both genotyped by polymerase chain reaction-ligase detection reaction(PCR-LDR)analysis.SPSS21.0 software package was used for statistical analysis(SPSS Company,Chicago,Illinois,USA).The age difference of cases and frequency-matched controls was analyzed by the t-test.Hardy-Weinberg analysis was performed by comparing the observed and expected genotype frequencies in the control group using the Chi-square test.Comparison of the genotype and allelotype distribution in patients and healthy controls was performed by means of two-sided contingency tables using Chi-square test and Fisher exact Probability.The odds ratio(OR)and 95% confidence interval(CI)were calculated using an unconditional logistic regression model.A probability level of 5% was considered significant for all statistical analyses.Results:1 The genotype frequencies of rs10965235C/A?rs2235529G/A in the healthy controls did not significantly deviate from that expected for a Hardy-Weinberg equilibrium(P=0.078;P=0.742).2 Genotype frequencies of the rs10965235 C/C,C/A and A/A in the cases were 69.8%,27.3%,2.9%,and 63.9%,33.5%,2.6% in the controls,respectively.The frequencies of the C and A alleles among case and control were 80.6,19.4 and 83.5,16.5%,respectively.There was no significant difference of genotype and allele frequency between the two groups(P=0.065 and P=0.072)(Table1),However,the C/A genotype may be a significantly decreased risk of developing ovarian endometriosis when compared with the C/C genotype(OR=0.74,95%CI=0.58-0.96)(Table2).3 The genotype frequencies of the rs2235529 A/A,A/G and G/G in the cases were 29.5%,49.0%,21.5%,and 25.9%,52.4%,18.1% in the controls,respectively.The frequencies of the A and G alleles among case and control were 54.0%,46.0% and 55.7%,44.3%,respectively.There was no significant difference of genotype and allele frequency between the two groups(P=0.308 and P=0.420)(Table1).Compared with the A/A genotype,the A/G and G/G genotypes was not associated with the risk of developing ovarian endometriosis:P= 0.125(OR=1.28,95%CI=0.94~1.72);P=0.329,(OR =1.18,95%CI= 0.85~1.69)(Table2),respectively.Conclusions:1 The single nucleotide polymorphism of rs10965235C/A may be a potential risk molecular markers in the patients with ovarian endometriosis in northern China Women.2 The results demonstrated the rs2235529G/A polymorphism was not likely associated with ovarian endometriosis in women from the North of China.