Tumor necrosis factor α and lymphotoxin α haplotypes in idiopathic recurrent pregnancy loss

ObjectiveTo investigate the contribution of the −238G/A and −308G/A tumor necrosis factor (TNF) α, and +252A/G lymphotoxin (LT) α gene polymorphisms to idiopathic recurrent miscarriage (RM).DesignA retrospective case-control study.SettingOutpatient 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 TNFα and LTα gene variants and idiopathic RM.Result(s)Higher prevalence of TNFα −238A and LTα +252G alleles and LTα +252G/G genotype and lower frequencies of TNFα −308G/A were seen in RM cases. Three-loci haplotype analysis (TNFα −308GA/TNFα −238GA/LTα +252AG) demonstrated significant association between TNFα-LTα 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 TNFα and LTα genotypes or haplotypes were linked with either late or combined early and late RM.Conclusion(s)The TNFα −238G/A and LTα +252A/G, but not TNFα −308G/A, polymorphic variants are associated with exclusively early idiopathic RM.