Association Of NOS3,IL-1β Gene Polymorphisms With Unexplained Recurrent Spontaneous Abortion

ObjectiveThe association between NOS3 and IL-1β gene polymorphisms and unexplained recurrent spontaneous abortion(URSA)was analyzed.To explore the single nucleotide polymorphism(SNP)sites of NOS3 and IL-1β genes with potential risk for URSA,in order to provide theoretical basis for the pathogenesis of URSA.MethodsA case-control study was conducted in this study.According to the inclusion and exclusion criteria,150 patients with recurrent abortion of unknown cause treated in the outpatient department of Maternal and Child-care Hospital of Gansu Province from January 2019 to August 2020 were selected as case group(URSA group),and 150 healthy women treated in physical examination center during the same period were selected as control.Blood samples were collected and genomic DNA was extracted.The genotypes and alleles of NOS3 gene rs2070744,IL-1β gene rs1143627,rs1143634 and rs16944 in URSA group and control group were detected by SNa Pshot multiple SNP typing technique.Statistical software was used to analyze the correlation between various gene polymorphic loci and recurrent abortion.P <0.05 was significantly difference.ResultsIn the control group,the distribution of NOS3 gene rs2070744,IL-1β gene rs16944,rs1143634,rs1143627 loci were in accordance with Hardy-Weinberg equilibrium(HWE)test(P > 0.05).Genotype and allele frequency distribution showed that the rs2070744 locus of NOS3 gene had statistically significant differences in genotype and allele frequency distribution between RSA group and control group(P=0.013,P=0.004).There was no statistical significance in the frequency distribution of genotype and allele at rs16944,rs1143634,rs1143627 of IL-1β gene(P > 0.05).Codominant genetic model of rs2070744 locus of NOS3 gene Optimal genetic model for this locus(AIC=412.2).In the co-dominant model,the risk of C/T was reduced by 0.37 times compared with TT type(OR C/T vs T/T =0.37,95%CI=1;P=0.0012).There was gene-gene interaction among the gene models,rs2070744 of NOS3 gene and rs16944,rs1643634 and rs1634627 of IL-1β gene were detected in three gene models:rs2070744,rs1143634-rs2070744,rs1143627-rs1143634-rs2070744,and P values were0.0103,0.0067,0.0027.Respectively,rs2070744 was the best model of gene-gene interaction.rs1143634 and rs2070744 had synergistic effects in the gene-gene interaction model.IL-1β gene rs16944,rs1143634 and rs1143627 were not associated with URSA.However,the interaction between IL-1β gene rs1143627 SNP and age was statistically significant(P <0.05).ConclusionsThe T/T genotype of rs2070744 in NOS3 gene may be associated with the risk of URSA,and NOS3 gene may be a genetic susceptibility gene for URSA.The codominant genetic model of NOS3 gene rs2070744 was the optimal genetic model for this locus.Its codominant,dominant,recessive and superdominant genetic models are all related to the risk of RSA.There were gene-gene interactions between NOS3 gene rs2070744 and IL-1β gene rs16944,rs1643634 and rs1634627.rs2070744 was the best model for gene-gene interaction.There was a synergistic effect between rs1143634 and rs2070744 in gene-gene interaction model.There was no correlation between IL-1β gene rs16944,rs1143634,rs1143627 and URSA,but there was gene-environment interaction between IL-1β gene rs1143627 SNP and age.