Maternal medication use, fetal 3435 C>T polymorphism of the ABCB1 gene, and risk of isolated septal defects in a Han Chinese population.

The fundamental etiology of the majority of nonsyndromic congenital heart defects is commonly believed to involve the interaction of multiple environmental and genetic factors. This study aimed to explore the joint effects of fetal 3435 C>T polymorphism in the ABCB1 gene and maternal medication use on the risk of septal defects in a Han Chinese population. An age- and gender-matched case-control study involving 265 pairs was conducted from March 2012 to September 2013. Information on maternal periconceptional medication use was obtained through questionnaires. The genotyping of 3435 C>T polymorphism was performed by sequencing. Logistic regression analysis was performed to assess the joint effects of ABCB1 gene 3435 C>T polymorphism and maternal medication use on the risk of septal defects. Use of maternal medication periconceptionally was significantly associated with an increased risk of septal defects [adjusted odds ratio (OR) 2.133; 95 % confidence interval (CI) 1.361-3.444; P = 0.001)]. The genotype distributions of 3435 C>T polymorphism differed significantly between cases and control subjects (P < 0.001). Meanwhile, more patients were carriers of the ABCB1 CC/CT genotypes, which were significantly associated with an increased risk of septal defects (OR 2.414; 95 % CI 1.418-4.110; P = 0.001). Children who carry the CC/CT genotype and have been exposed periconceptionally to medication have an almost fourfold increased risk of having septal defects than nonexposed children with the TT genotype (adjusted OR 3.932; 95 % CI 1.708-9.051), particularly perimembranous ventricular septal defects (VSD) (adjusted OR 4.070; 95 % CI 1.570-10.552). In conclusion, fetal 3435 C>T polymorphism in the ABCB1 gene increases the risk for isolated septal defects in the presence of maternal medication use periconceptionally, particularly for perimembranous VSD.