Effect of the TNF α-308 polymorphism on birth outcomes among South African women

Abstract

The −308 G/A promoter polymorphism in the tumor necrosis factor-alpha (TNF- α) gene has been extensively studied as a potential biomarker for pregnancy outcomes, but results tend to be population specific. The aim of this study was to evaluate the association of the TNF α-308 polymorphism with preterm birth (PTB) and low birth weight (LBW) in a cohort of South African women enrolled in a prospective pregnancy study. The Mother and Child Environmental cohort (MACE) pilot study was done in Durban, KwaZulu-Natal during 2010-2011 with 100 pregnant women recruited. Demographic, exposure and prenatal clinical data was collected during the third trimester, maternal and infant hospital records at delivery were reviewed. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine the TNF-α -308 genotype. Plasma TNF-α concentration was measured using the human TNF-α Max Standard™ ELISA kit (Bio-legend). The polymorphic TNF-α GA+AA genotype was found among 35% of mothers. Mean birth weight was significantly lower among mothers with the TNF-α AG+AA genotype (p<0.05). Mothers who delivered LBW infants (<2500g) showed a significantly higher mean TNF- α level compared to mothers with normal birth weight deliveries. In addition, mothers with the TNF-α AG+AA genotype had a statistically significant drop in birth weight (β= -273.6; SE105.8; CI: -0.9,-1.35). While the TNF-α A allele was not associated with PTB, it was significantly associated with low birth weight in this study. Early identification of such immunological biomarkers may facilitate prevention of adverse pregnancy outcomes.