A medical molecular genetics of Orofacial clefting: Role of ABC Transporter Polymorphisms in Disease Risk

Abstract

Family based association and case-control studies were conducted to investigate the role of potentially functional polymorphisms within four ABC transporters' genes, namely ABCB1 (e12/C1236T, e21/G2677T/A, e26/C3435T), ABCC1 (5'FR/G-260C), ABCC2 (e1/C-24T, e10/G1249A, e25/G3542T), and ABCG2 (e2/G34A, i9/T-357C, e5/C421A) in susceptibility to orofacial clefting. In the family based study, 150 nuclear families of single affected offspring with oral clefts participated from Singapore and Taiwan. The case-control study consisted of 128 Chinese oral cleft children recruited in the family based study and controls were cord blood DNA samples from 189 healthy Chinese mothers. Extracted genomic DNAs from blood samples were genotyped for target SNPs. An extended transmission disequilibrium analysis on the families' genotype data revealed that only SNPs within the ABCB1 gene (e12/1236, e21/2677, and e26/3435), but not SNPs in other ABC genes were significantly associated with oral clefting (P<0.05). This finding was interestingly validated by the case-control study using Fisher's exact test.