Objective: To investigate the contribution of the -238G/A and -308G/A tumor necrosis factor (TNF) alpha, and +252A/G lymphotoxin (LT) alpha gene polymorphisms to idiopathic recurrent miscarriage (RM).
Design: A retrospective case-control study.
Setting: Outpatient maternity center.
Patient(s): Study subjects comprised 372 RM women and 274 age-matched parous control women.
Intervention(s): None.
Main outcome measure(s): The TNFalpha and LTalpha gene variants and idiopathic RM.
Result(s): Higher prevalence of TNFalpha -238A and LTalpha +252G alleles and LTalpha +252G/G genotype and lower frequencies of TNFalpha -308G/A were seen in RM cases. Three-loci haplotype analysis (TNFalpha -308GA/TNFalpha -238GA/LTalpha +252AG) demonstrated significant association between TNFalpha-LTalpha gene variants and RM. Both protective [-308A/-238G/+252A], and susceptible [-308G/-238A/+252G] haplotypes were identified. Mutlivariate regression analysis confirmed the association of -308G/-238A/+252G haplotype with exclusively early RM, after controlling for a number of covariates; no specific TNFalpha and LTalpha genotypes or haplotypes were linked with either late or combined early and late RM.
Conclusion(s): The TNFalpha -238G/A and LTalpha +252A/G, but not TNFalpha -308G/A, polymorphic variants are associated with exclusively early idiopathic RM.