508b4197-20f3-4834-ac8c-f3ba889ff80f
title
Association between nonsyndromic cleft lip with or without cleft palate and the  glutamic acid decarboxylase 67  gene in the Japanese population.
ef5e8e0d-f01b-4cf2-9b4b-e91b3c8d2ee3
abstract
Nonsyndromic cleft lip with or without cleft palate (NSCLP) is one of the most common craniofacial malformations. Both genetic and environmental factors are involved in the pathogenesis. In addition to its role as an inhibitory neurotransmitter, gamma-aminobutyric acid (GABA) synthesized by glutamic acid decarboxylase (GAD) is presumed to play a role in normal embryonic, especially facial, development. This notion has been substantiated by the fact that Gad67 knockout mice have been shown to have cleft palate. We hypothesized that  GAD67  may be involved in the development of NSCLP and investigated the possible association between the  GAD67  gene ( GAD67 ) and NSCLP in Japanese patients. We screened 50 probands for single nucleotide polymorphisms (SNPs) in  GAD67  using denaturing high performance liquid chromatography (DHPLC) and found seven SNPs. Since two SNPs showed complete linkage disequilibrium (LD) to the other SNPs, we constructed a 5-locus haplotype of  GAD67 . The frequency distribution of the haplotype differed between NSCLP patients and controls (P = 0.0028). The frequency of  -445A ,  -292A ,  -147G ,  111C , and  IVS9-39T  haplotype in the NSCLP patients was significantly lower than that in controls (P = 0.00098). In a transmission disequilibrium test (TDT) in 99 parent-offspring trios, we found  -445C ,  -292C ,  -147G ,  111C , and  IVS9-39C  haplotype was preferentially transmitted to the patients with cleft lip and palate (P = 0.0077). Our data suggest that  GAD67  is involved in the pathogenesis of NSCLP in the Japanese population.