Association of the neuronal nicotinic acetylcholine receptor subunit alpha4 polymorphisms with febrile convulsions.
OBJECTIVE
The alpha4-subunit gene of the neuronal nicotinic acetylcholine receptor (CHRNA4) has been identified as the first gene underlying an idiopathic partial epilepsy syndrome in human autosomal-dominant nocturnal frontal lobe epilepsy. Studies provided evidence that the protein coded by CHRNA4 is one of the most abundant subunits of the neuronal nicotinic acetylcholine receptors in mammalian brains, and mutations of CHRNA4 seem to cause neuronal excitation. The CHRNA4 gene may have a role in the development of febrile convulsions (FCs), the majority of childhood seizures. This study assessed the distribution of genotypes of CHRNA4 in patients with FCs.


METHODS
A total of 102 children with FCs and 80 normal control subjects were included in the study. Polymerase chain reaction was used to identify the C/T polymorphism of the CHRNA4 gene. Genotypes and allelic frequencies for the CHRNA4 gene polymorphisms in both groups were compared.


RESULTS
The number of individuals with heterozygous CHRNA4 (Ser543Ser)-C/T genotype was significantly greater (60.8% vs. 32.5%; p = 0.001), and the CHRNA4 (Ser543Ser)-T allele frequency was significantly higher (p = 0.001), in patients with FCs compared with healthy controls. The odds ratio for developing FCs in individuals with the CHRNA4 (Ser543Ser)-CT genotype was 3.77 compared with individuals with two copies of the CHRNA4 (Ser543Ser)-C allele.


CONCLUSIONS
This study demonstrated an association between the CHRNA4 gene and FCs. Individuals with the T allele had a higher incidence of FCs. These data suggest that the CHRNA4 gene or a closely linked gene might be one of the susceptibility factors for FCs.
Chou
I-Ching
IC
Pediatrics Neurology, China Medical College Hospital, Taichung, Taiwan.
Lee
Cheng-Chun
CC
Huang
Chao-Ching
CC
Wu
Jer-Yuarn
JY
Tsai
Jeffrey J P
JJ
Tsai
Chang-Hai
CH
Tsai
Fuu-Jen
FJ
D000483:Alleles; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006580:Genetic Carrier Screening; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011978:Receptors, Nicotinic / Q000235:genetics*; D003294:Seizures, Febrile / Q000175:diagnosis / Q000235:genetics*; D013624:Taiwan
D005819:Genetic Markers; D011978:Receptors, Nicotinic