The Association Between Polymorphisms Of Genes Related To Inflammation And Recurrent Pregnancy Loss Susceptibility

Objective: Recurrent pregnancy loss(RPL)is usually defined as three or more consecutive idiopathic miscarriages before 28 weeks.The aim of this study is to evaluate the relationship between polymorphisms of genes related to inflammation and recurrent pregnancy loss susceptibility,some immunological candidate genes including FOXP3,CTLA4,CX3CR1,FAU,IL-21,CCR5 and IL-18.Methods: In this work,the case group include 107 patients with recurrent pregnancy loss chosen in the Family Planning Department of the second Hospital of Tianjin Medical University from September 2014 to November 2016.The control group consist of 187 healthy women from the Family Planning Department of the second Hospital of Tianjin Medical University in the same time.Genotyping of the FAU gene polymorphisms rs769440 was examined by utilizing the combine of polymerase chain reaction and direct sequencing,the other candidate genes were used of the Sequenom Mass ARRAY system.Hardy-Weinberg equilibrium and the comparisons of genotype and allele frequencies between RPL case and control were performed on the online software SHEsis by chi-square test.The linkage disequilibrium statistics were computed using D' and r2 on Haploview Ver.3.32.Haplotype distribution was estimated using the program UNPHASE.Genetic power was calculated using the Quanto(http://biostats.usc.edu/software).Results:(1)The genotype distributions of the polymorphism both in case and control group were all in Hardy-Weinberg equilibrium(P>0.05),it is explained that the samples which we choosen in our study has group representative.(2)The FAU rs769440 C/G allele in case-control group were 129/85 and 242/135,the FAU rs769440 G allele had higher frequencies in patients with RPL susceptibility(P=0.019).(3)No association was observed between other polymorphisms and RPL susceptibility.FOXP3 rs2232365(A/G,P=0.968),CTLA4 rs231775(A/G,P=0.533),CX3CR1 rs3732378(A/G,P=0.716),CX3CR1 rs3732379(C/T,P=0.73),IL-21 rs13143866(A/G,P=0.266),CCR5 rs1799987(C/T,P=0.593)and IL-18 rs360718(A/G,P=0.966)?(4)Assess the extent of linkage disequilibrium in combination of the SNPs,the results showed that the pairwise D' value were from 0.98 to 1 for FOXP3 rs2232365,CTLA4 rs231775,CX3CR1 rs3732378,CX3CR1 rs3732379 and FAU rs769440.(5)Performed haplotype analyses of FOXP3 rs2232365,CTLA4 rs231775,CX3CR1 rs3732378,CX3CR1 rs3732379 and FAU rs769440 polymorphisms,there was no significant difference among the haplotypes.Conclusions:(1)The results showed an association between FAU rs769440 polymorphism and RPL in Chinese Han population.(2)FOXP3 rs2232365,CTLA4 rs231775,CX3CR1 rs3732378,CX3CR1 rs3732379,IL-21 rs13143866,CCR5 rs1799987,IL-18 rs360718 polymorphism has no association with RPL.