Contribution of functional IL-18 promoter polymorphisms to the risk of idiopathic recurrent spontaneous miscarriage (117.29)

Abstract

Abstract Interleukin (IL)-18 is a proinflammatory cytokine, which modulates Th1 differentiation and CTL effector activity, both of which were implicated in the pathogenesis of recurrent spontaneous miscarriage (RSM). We evaluate the association of single nucleotide polymorphisms (SNPs) in the IL18 gene promoter at -656G/T (rs1946519),-137G/C (rs187238), -119T/G (rs360718), and -105T/C (rs360717), were detected by TaqMan assays in analysis in 277 RSM cases and 283 control women matched for age and ethnic background; serum IL-18 level was measured by ELISA. Association of IL-18 alleles, genotypes, and haplotypes with RSM were evaluated by Fisher's exact test and regression analysis. The -656T (P<0.001; OR, 1.87; 95% CI, 1.44-2.42) and -105C (P<0.001; OR, 2.00, 95% CI, 1.54-2.59) alleles, significantly increased RSM risk. Significant differences in the distribution of -656G/T and -105T/C genotypes were seen between RSM cases and controls; no association was found between -137G/C or -119T/G and RSM. Haploview analysis revealed linkage disequilibrium between VEGF SNPs analyzed SNPs. Four-locus (rs1946519/rs187238/rs360718/rs360717) haplotype analysis identified two RSM-protective (1111 and 1222) and two RSM-susceptible (1112 and 2112) haplotypes. Multivariate analysis confirmed the positive association of 2112 haplotype with RSM, after controlling for a number of covariates. These results demonstrate that the VEGF polymorphisms are significantly associated with idiopathic RSM.