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

Context: CTLA-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-alpha known as an embryo-toxic cytokine is reported to be greater in placentas of abortion prone pregnancies. Objectives: The present study investigated the role of CTLA-4 +49 A/G, CTLA-4 (AT)(m)3'UTR,TNF-alpha-308G/A and TNF-alpha-238G/A polymorphisms as a susceptibility marker for recurrent miscarriage (RM). Participants and methods: We genotyped CTLA4 +49A/G, TNF-alpha-308 and TNF-alpha-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. Results: The mutant homozygous genotype GG of CTIA4 +49A/G, AA genotype and A allele of TNF-alpha-308, G allele of TNF-alpha-238 were observed to be predisposing among RM cases along with the 104 bp, 106 bp, 110 bp and 116 bp alleles of CTLA-4 (AT)(n) microsatellite repeat. GA and AG haplotypes of TNF-alpha were low risk associated haplotypes among recurrent miscarriage women. Conclusions: Roles of CTLA-4 A49G, CTLA-4 (AT)(n) 3'UTR, TNF-alpha-308 and TNF-alpha-238 polymorphisms in RM cases from North India is reflected through this study. (C) 2012 Elsevier Ltd. All rights reserved.