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

Research Unit of Haematological and Autoimmune Diseases, Faculty of Pharmacy, University of Monastir, Monastir, Tunisia¹ CHU Frahat Hached, Sousse, Tunisia² Faculty of Biological and Pharmaceutical Sciences, Montpellier-1 University, Montpellier, F- 30029 France and³ Department of Medical Biochemistry, College of Medicine and Medical Sciences, Arabian Gulf University, PO Box 22979, Manama, Bahrain

Correspondence should be addressed to W Y Almawi; Email: wassim{at}agu.edu.bh

Heightened expression of tumor necrosis factor (TNF)- and lymphotoxin- (LT-) was associated with pregnancy complications, including idiopathic recurrent miscarriage (RM). Whereas TNF- and LT- gene polymorphisms affect serum cytokine concentrations, their contribution to RM is controversial. The single nucleotide polymorphisms (SNPs) TNF- (–238G/A, –308G/A) and LT- (+252A/G) were investigated in 350 RM women and 200 control women. Higher frequency of the TNF- –238A, but not the TNF- –308A or the LT-+252G, allele was seen in patients, with comparable frequencies of TNF- –238G/A, TNF- –308G/A, and LT-+252A/G genotypes seen between both groups, except for TNF- –238G/G, which was lower in patients. Regression analysis confirmed the association of the TNF- –238G/A SNP with idiopathic RM, and both TNF- –308A/TNF –238G/LT-+252G and TNF- –308G/TNF- –238A/LT-+252G haplotypes played a susceptible role in idiopathic RM. TNF- –238G/A and –238A/A, and LT-+252G/G genotypes were positively associated only with exclusively early RM. This supports the concept of the association of TNF- (–238G/A) and LT- (+252A/G) polymorphic variants in idiopathic RM.