Association of the GABRB3 gene with nonsyndromic oral clefts.
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, gamma-aminobutyric acid plays a role in normal embryonic, and particularly facial, development and gamma-aminobutyric acid receptor type A beta-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.


METHODS
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.
Inoue
Hiroki
H
Department of Public Health, Chiba University Graduate School of Medicine, Chiba, Japan.
Kayano
Shuji
S
Aoki
Yoko
Y
Kure
Shigeo
S
Yamada
Atsushi
A
Hata
Akira
A
Matsubara
Yoichi
Y
Suzuki
Yoichi
Y
D016022:Case-Control Studies; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D018900:Dinucleotide Repeats; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007564:Japan; D020641:Polymorphism, Single Nucleotide; D011963:Receptors, GABA-A / Q000235:genetics*
C546273:GABRB3 protein, human; C546270:Gabrb3 protein, mouse; D011963:Receptors, GABA-A