Associations between tumor necrosis factor-a and lymphotoxin-a polymorphisms and idiopathic recurrent miscarriage

Abstract

Heightened expression of tumor necrosis factor (TNF)-a and lymphotoxin-a (LT-a) was associated with pregnancy complications, includingidiopathic recurrent miscarriage (RM). Whereas TNF-a and LT-a gene polymorphisms affect serum cytokine concentrations, their contribution to RM is controversial. The single nucleotide polymorphisms (SNPs) TNF-a (K238G/A, K308G/A) and LT-a (C252A/G) were investigated in 350 RM women and 200 control women. Higher frequency of the TNF-a K238A, but not the TNF-a K308A or the LT-aC 252G, allele was seen in patients, with comparable frequencies of TNF-a K238G/A, TNF-a K308G/A, and LT-aC252A/G genotypes seenbetween both groups, except for TNF-a K238G/G, which was lower in patients. Regression analysis confirmed the association of the TNF-a K238G/A SNP with idiopathic RM, and both TNF-a K308A/TNF K238G/LT-aC252G and TNF-a K308G/TNF-a K238A/LT-aC252G haplotypes played a susceptible role in idiopathic RM. TNF-a K238G/A and K238A/A, and LT-aC252G/G genotypes were positively associated only with exclusively early RM. This supports the concept of the association of TNF-a (K238G/A) and LT-a (C252A/G) polymorphic variants in idiopathic RM.