Abstract
BackgroundApproximately half of recurrent miscarriages have unexplained etiology. Recent evidences suggest that cytokines are important determinants in pregnancy maintenance and as such, cytokine gene polymorphisms, which can affect cytokine production and/or functionality, could play a role in the disorder. Thus, we aimed to investigate the association of selected cytokine gene polymorphisms with risk of recurrent miscarriage among Chinese.MethodsTNF -238G > A, TNF -308G > A, IL1B -511 T > C, IL1B 3954C > T, IL6 -174G > C, IL6 -634C > G, IL10 -1082A > G and IFNG 874A > T polymorphisms were genotyped on 775 women with idiopathic recurrent miscarriage and 805 healthy parous control women. Logistic regression analysis was performed to determine the odds ratios (ORs) of the association between the polymorphisms and recurrent miscarriage risk.ResultsAmong the eight polymorphisms studied, only the IL1B -511 T > C and IL6 -634C > G polymorphisms showed statistically significant associations with recurrent miscarriage risk. For the former, a significantly increased risk of recurrent miscarriage was observed for the mutant (CC) genotype (OR: 1.377; 95% CI: 1.039–1.824; P = 0.026). However, for the IL6 -634C > G polymorphism, a decreased recurrent miscarriage risk was observed for the heterozygous (CG) genotype (OR: 0.614; 95% CI: 0.493–0.765; P < 0.001) and the mutant (GG) genotype (OR: 0.414; 95% CI: 0.251–0.684; P = 0.001).ConclusionsThe IL1B -511 T > C polymorphism may serve as important risk factor for recurrent miscarriage while the IL6 -634C > G polymorphism may protect against the risk of recurrent miscarriage.
Highlights
Half of recurrent miscarriages have unexplained etiology
We investigated the association of eight selected cytokine gene polymorphisms with risk of recurrent miscarriage among Chinese women
Significant difference in the distribution of genotypes between the cases and controls was only observed for the IL6 -634C > G polymorphism (P < 0.001), with the wild type (CC) genotype observed to be overrepresented in the cases and the heterozygous (CG) and mutant (GG) genotypes observed to be overrepresented in the controls
Summary
Recent evidences suggest that cytokines are important determinants in pregnancy maintenance and as such, cytokine gene polymorphisms, which can affect cytokine production and/or functionality, could play a role in the disorder. Recurrent miscarriage refers to the consecutive loss of pregnancy before the 20th gestational week for three or more times [1]. This event affects approximately 1–2% of otherwise healthy females, and poses a significant physical and emotional burden on women experiencing the incidence and their family members [2]. During early stages of normal pregnancies, pro-inflammatory T helper (Th) 1 cytokines are necessary for stimulating vasculogenesis which is essential for a successful embryonic implantation [4]. The proper homeostatic balance between Th1 and Th2 cytokines is
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