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Analysis of CCR5 and CX3CR1 gene polymorphisms in association with unexplained recurrent miscarriages among north Indian women
Authors:Parveen F  Faridi R M  Singh B  Agrawal S
Institution:Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, UP, India
Abstract:

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.
Keywords:Pregnancy  Recurrent miscarriage  CCR5  CX3CR1  Polymophism
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