Objective: Nonsyndromic oral clefts are common craniofacial anomalies classified into two subgroups: cleft lip with or without cleft palate and isolated cleft palate. Nonsyndromic oral clefts are multifactorial diseases, with both genetic and environmental factors involved in their pathogenesis. The inhibitory neurotransmitter, γ-aminobutyric acid plays a role in normal embryonic, and particularly facial, development and γ-aminobutyric acid receptor type A β-3 subunit (GABRB3) knockout mice have been shown to have cleft palate. The GABRB3 gene is therefore a strong candidate gene for nonsyndromic oral clefts. We investigated here whether genetic variations of the GABRB3 gene affect the risk for nonsyndromic oral clefts. Method: In this case-control study, a total of 178 Japanese patients with cleft lip with or without cleft palate and 374 unrelated controls were recruited and were genotyped for six single nucleotide polymorphisms and a dinucleotide repeat marker of the GABRB3 gene. Results: None of the single nucleotide polymorphisms showed complete linkage disequilibrium with other single nucleotide polymorphisms. In a case-control association study with the six-locus haplotype of the gene, TGTGCT haplotype frequency in patients with cleft lip with or without cleft palate was significantly higher than in the controls (corrected p value = .029). None of the alleles of the dinucleotide repeat marker showed significant association with cleft lip with or without cleft palate. Conclusions: Our data suggest that the GABRB3 gene is involved in the pathogenesis of cleft lip with or without cleft palate in the Japanese population.
ASJC Scopus subject areas