Association of CTLA-4 and TNF-α polymorphism with recurrent miscarriage among North Indian women

Abstract

ContextCTLA-4 is engaged on effector cells that may alter signal transduction and subsequently cytokine production. The transmission of longer repeats of (AT)n alleles of CTLA-4 is also associated with women undergoing recurrent miscarriage. The TNF-α known as an embryo-toxic cytokine is reported to be greater in placentas of abortion prone pregnancies. ObjectivesThe present study investigated the role of CTLA-4+49 A/G, CTLA-4 (AT)n 3′UTR, TNF-α-308G/A and TNF-α-238G/A polymorphisms as a susceptibility marker for recurrent miscarriage (RM). Participants and methodsWe genotyped CTLA4+49A/G, TNF-α-308 and TNF-α-238 gene polymorphisms in 300 patients with RM and 500 age and ethnically matched negative controls using PCR–RFLP method. While gene sequencing method was adopted for studying the CTLA-4 (AT)n 3′UTR polymorphism. ResultsThe mutant homozygous genotype GG of CTLA4+49A/G, AA genotype and A allele of TNF-α-308, G allele of TNF-α-238 were observed to be predisposing among RM cases along with the 104bp, 106bp, 110bp and 116bp alleles of CTLA-4 (AT)n microsatellite repeat. GA and AG haplotypes of TNF-α were low risk associated haplotypes among recurrent miscarriage women. ConclusionsRoles of CTLA-4 A49G, CTLA-4 (AT)n 3′UTR, TNF-α-308 and TNF-α-238 polymorphisms in RM cases from North India is reflected through this study.