Correlation Study On Single Nucleotide Polymorphism Of Fibulin-5 And Genetic Predisposition Of Pelvic Organ Prolapse

Objective: To explore the correlation between the single nucleotide polymorphism (SNP) of fibulin-5 and genetic predisposition of pelvic organ prolapse (POP), which aims to provide scientific basis for the prevention of disease.Methods: From Septemper 2009 to December 2010, 279 patients who came to gynaecology and obstetrics department of Fuzhou General Hospital of Nanjing Military Command for certain treatments were selected,including 19 familial POP, 91 sporadic POP,and172 controls. Blood samples were collected from the all,but only 72 patients who needs surgery donated their vaginal wall tissues. After extracting DNA from blood, the promoter,11 exons (containing the 200bp in.two wings) of fibulin-5 were sequenced in familial POP in order to detect mutant and select the high frequency SNP.Then MALDI-TOF-MS was used to detect the genotype of selected SNP in all patients.Chi-square test was done to analyse the Hardy-Weinberg equilibrium,and compare the genotype frequency difference between the patients and controls,while Logistic regression was used to analyse the relationship between SNP and POP. Subsequently, the mRNA expression of fibulin-5 was detected in the tissues by RT-PCR, and then the relationship between that and POP as well as SNP genotype was analysed by partial correlation analysis.Results: 6 high frequency SNP were detected from the familial POP, which were rs2474030,rs7149187,rs2474028,rs35187606,rs2430347,rs929608.After genotyping the other patients,only rs7149187,rs2474028 and rs929608 had sigificant differences in genotype frequency between patients and controls. Logistic regression showed that genotype AA of rs7149187,TT of rs2474028,CC of rs929608 could increase the risk of POP (P<0.05).Besides, there was strong linkage disequilibrium among rs2474030,rs7149187,rs2474028, and the haplotype AGT may increase the risk of POP(OR=11.101,P=0.002). In addition, there was no difference in mRNA expression of fibulin-5 between cases an controls,while significant differences were detected among SNP genotypes. Genotype AA of rs7149187 displayed relatively higher ratios(P=0.015), which reflected the down-expression of fibulin-5 mRNA .Conclusion: There was correlation between SNP of fibulin-5 and susceptibility to POP. Genotype AA of rs7149187,TT of rs2474028,CC of rs929608 and the haplotype AGT could increase the risk of POP, so they maybe the risk factors of POP. Expression of fibulin-5 mRNA probably irrelevant with POP ,while some relevance was observed between that and polymorphism of rs7149187.The transition G>A of rs7149187 may interference the combination of AP-2 with DNA ,and result in the down-regulation of fibulin-5 mRNA expression,which could reduce the formation of elastic fiber,and last increase the risk of POP. Therefore, genotype AA of rs7149187 may be an important index in the detection of the genetic predisposition to pelvic organ prolapse.