Case-control study and transmission/disequilibrium tests of the genes encoding GABRA5 and GABRB3 in a Chinese population affected by childhood absence epilepsy / 中华医学杂志(英文版)

ABSTRACT

<p><b>BACKGROUND</b>Childhood absence epilepsy (CAE) is one of the most frequently recognized syndromes among the idiopathic generalized epilepsies (IGEs). CAE is considered to be a genetic disease, with a possible polygenic inheritance pattern. The genes responsible for CAE have not been identified yet. The object of this study was to investigate whether or not CAE is associated with the gene encoding the gamma-aminobutyric acid (GABA) type-A receptor subunits alpha5 (GABRA5) and beta3 (GABRB3) in a Chinese population.</p><p><b>METHODS</b>Five microsatellite DNA repeats, 69CA, 85CA, 155CA1, 155CA2, and A55CA1, adjoining chromosome 15q11-q13, were used as genetic markers. Both case-control study and transmission/disequilibrium tests (TDTs), as well as fluorescence-based semi-automated genotyping techniques, were used in 90 CAE patient-mother-father trios and 100 normal controls of Han ethnicity to conduct association analysis.</p><p><b>RESULTS</b>The frequencies of allele 5 of 69CA, alleles 2 and 8 of 85CA, alleles 6 and 7 of 155CA1, allele 2 of 155CA2, and alleles 1 and 11 of A55CA1 were significantly higher in CAE patients than in normal controls. To prevent spurious associations arising from population admixture, we further conducted TDT tests in the 90 CAE trios. The results of TDT analysis further suggested that microsatellite DNA repeats 85CA, 155CA1, and 155CA2 were associated with CAE.</p><p><b>CONCLUSIONS</b>GABA type-A receptor subunit genes GABRA5 and GABRB3 may be either directly involved in the etiology of CAE in the Chinese population or in linkage disequilibrium with disease-predisposing sites.</p>