Association between IL-6-174 G/C, IL-6-634 G/C, and IFN-gamma+874 A/T polymorphisms and susceptibility to recurrent pregnancy loss: a meta-analysis

Abstract

The aim of this study was to determine whether interleukin-6 (IL-6) -174 G/C, IL-6 -634 G/C, and interferon-gamma (IFN-gamma) +874 A/T polymorphisms are associated with susceptibility to recurrent pregnancy loss (RPL). We conducted a literature search using PubMed and EMBASE databases and performed a meta-analysis using fixed- or random-effects models. A total of 15 articles met the study inclusion criteria. When all study subjects were considered together, meta-analysis showed no association between RPL and the IL-6 -174 GG + GC genotype (odds ratio [OR] = 0.794, 95 % confidence interval [CI] = 0.542-1.163, p = 0.236). However, stratification of the data by ethnicity indicated an association between this genotype and RPL in non-Caucasians (OR = 0.528, 95 % CI = 0.302-0.925, p = 0.028), but not in Caucasian populations. Moreover, meta-analysis revealed an association between RPL and the IL-6 -634 GG + GC genotype in all study subjects (OR = 0.556, 95 % CI = 0.383-0.806, p = 0.002), while stratification by ethnicity revealed a negative association between this genotype and RPL in Asian (OR = 0.545, 95 % CI = 0.371-0.800, p = 0.002) but not Middle Eastern populations. Furthermore, a relationship between the IFN-gamma +874 A allele and RPL was identified in non-Caucasians (OR = 1.403, 95 % CI = 1.133-1.734, p = 0.002), but not in Caucasians. This meta-analysis demonstrates that IL-6 -174 G/C, IL-6 -634 G/C, and IFN-gamma +874 A/T polymorphisms are associated with susceptibility to RPL, particularly in non-Caucasians.