Association Of The VEGF Gene Polymorphism With The Recurrent Spontaneous Abortion

Objective: To investigate the correlation between4SNPs (rs699947, rs1570360,rs833061, rs3025039) polymorphisms of the vascular endothelial growth factor (VEGF) geneand recurrent spontaneous abortion (RSA) in Chinese Han women of Ning Xia populations.By comparing the genotype distribution and allele frequency between the patient of recurrentspontaneous abortion (RSA) and normal pregnancy women,to approach the relationship aboutthe haplotype of four SNPs of the vascular endothelial growth factor gene with RSA.Methods:203patients of RSA were recruited from Ning Xia medical university geneticlaboratory as study group with an average age of27.63±4.44.190normal pregnancy womenfrom Maternal and Child Health Hospital were as control group with an average age of27.26±2.31. The Polymerase Chain Reaction-Restriction Fragment Length Polymorphism(PCR-RFLP) and allele specific PCR (AS-PCR) were used to analyze the genotypedistribution and allele frequency of four SNPs in VEGF gene. The statistical analysis includedchi-square test and SPSS18.0software was used to analyze the data and calculated thedistribution of genotype and frequency of allele. Hardy-Weinberg balance and linkagedisequilibrium and haplotype analyzed by using software Haploview.Results:①The genotype distribution of the4SNPs in VEGF gene reachedHardy-Weinberg equilibrium except rs1570360, indicated that the population in present study were selected randomly.②There were significantly different in genotype distribution andallele frequencies of VEGF gene rs833061and rs3025039between the patient of RSA andnormal pregnancy women(P<0.001, P<0.01).③There were no significantly different ingenotype distribution and allele frequencies of VEGF gene rs699947, rs1570360between thepatient of RSA and normal pregnancy women (P>0.05).④Among the haplotypes establishedby the3SNPs, there were five kinds of protective haplotypes significantly different betweencase and control (P<0.05, OR<1), and five kinds of risk haplotypes also have significantdifference between case and control (P<0.05, OR>1).Conclusions:1.The polymorphisms of VEGF gene rs699947(C/A) and rs1570360(G/A)may not associated with the susceptibility of RSA in Ningxia female.2.VEGF geners833061(T/C) and rs3025039(C/T) polymorphisms may have some relevance with RSA;individuals who carry the genotype involved T allele, the risk of RSA may be increased inboth of two polymorphisms.3.The three SNPs in VEGF gene may have five kinds ofprotective haplotypes and five kinds of rise haplotypes. Objective: To assess and synthesis the available data from association studies of VEGFgene polymorphisms with RSA.Methods: After generally collecting the literatures published from open to2013thatreported on correlations between VEGF gene polymorphisms and RSA. Meta-analysis areprocessed using Review Manager5.2program, selecting fixed and random model test.Sensitivity analysis is done to the results from different "including standers", publication biasis evaluated by funnel plots.Results: We examined11published studies and1unpublished study, consisting11case-control comparisons about rs1570360(G/A) polymorphism,7case-control studies aboutrs699947(C/A) polymorphism and8case-control studies about rs3025039(C/T)polymorphismthat were based on our inclusion criterion and available in the literature. Test for heterogeneityof the various documents of rs699947, rs3025039study showed no significant heterogeneityand rs1570360was selected literature exists significant heterogeneity. Meta-analysis did notidentify any significant association with rs1570360and rs699947, the combined OR and95%confidence region are separately as following:1.16(0.96-1.41),1.01(0.78-1.30); but rs3025039somehow related to RSA, the combined OR and95%confidence region is1.33(1.11-1.60), P<0.05. According to the characters of the literatures, sensitivity analysis is carried out todifferent factors. Sensitivity analysis results are similar to the original results, which provethat the conclusion of this research work is stable and reliable.Conclusions: rs3025039(C/T) was related to RSA to some extent but rs1570360(G/A)and rs699947(C/A) have no significant correlation with RSA.The sensitivity analysis andpublication bias estimation show that the outcomes of this research work is stable and reliablewhich can authentically reflect the findings of VEGF (rs1570360, rs699947, rs3025039) withRSA relations in the latest decade.