Analysis of CCR5 and CX3CR1 gene polymorphisms in association with unexplained recurrent miscarriages among north Indian women.

摘要

CONTEXT: Recurrent miscarriage (RM), defined as three or more consecutive losses before the 20th week of gestation, affects 0.5-2% of pregnant women. In over 80% of cases, RM remains unexplained after investigations, suggesting the involvement of genetic factors. OBJECTIVES: The present study investigates the common polymorphisms of chemokine receptors CCR5 (NG_012637.1:g.5303A>G) and CX3CR1 (NG_016362.1:g.21065C>T, Thr280Met and NG_016362.1:g.20971G>A, Val249Ile) and their association with recurrent miscarriages (RM) among north Indian women. PARTICIPANTS AND METHODS: In a retrospective case-control study 200 well characterized patients with unexplained RM and 300 controls were genotyped for three polymorphic markers of CCR5 and CX3CR1 by restriction digestion of PCR amplified fragments. RESULTS: Alleles and genotypes of CX3CR1 Val249Ile revealed statistically significant associations with RM cases when compared with the controls. The homozygous variant genotype Ile/Ile was found to be significantly higher among patients (p=0.0002) when compared with the homozygous wild type Val/Val genotype. The haplotype of CX3CR1 that carried major alleles of Thr280Met and Val249Ile (T-V) showed statistically significant protective association (p<0.0001, OR=0.41, 95% CI=0.31-0.54). The haplotype A-T-V (all wild type alleles) revealed a statistically significant protective association (p<0.0001, OR=0.41, 95% CI=0.34-0.62), whereas the haplotypes G-T-I, A-T-I and A-M-V modified the risk of RM 1.9-fold, 5.5-fold and 5.1-fold respectively. CONCLUSIONS: A common polymorphism of CX3CR1 gene, Val240Ile is associated with the risk of RM in north Indian women. Risk of RM may also be modified by the presence of haplotypes T-I, M-V, G-T-I, A-T-I and A-M-V.