Association analysis of malic enzyme 2 gene polymorphisms with idiopathic generalized epilepsy.
OBJECTIVE
Linkage disequilibrium mapping revealed allelic and haplotypic associations between single-nucleotide polymorphisms (SNPs) of the gene encoding the malic enzyme 2 (ME2) and adolescent-onset idiopathic generalized epilepsy (IGE). Homozygote carriers of the associated ME2 haplotype had a sixfold higher risk of IGE compared with any other genotype. The present population-based association study tested whether genetic variation of the ME2 gene confers susceptibility to common IGE syndromes in the German population.


METHODS
The study included 666 German healthy control subjects and 660 German IGE patients (IGE group), of which 416 patients had an age at onset in adolescence (IGEado group). Genotyping was performed for six SNPs and one dinucleotide repeat polymorphism, all located in the ME2 region.


RESULTS
Neither allele nor genotype frequencies of any ME2 polymorphism differed significantly between the controls and the IGE groups (p > 0.22). No hint of an association of the putative risk-conferring haplotype was seen, when present homozygously, in both IGE groups compared with controls (p > 0.18).


CONCLUSIONS
These results do not support previous evidence that genetic variation of the ME2 gene predisposes to common IGE syndromes. Thus if a recessively inherited ME2 mutation is present, then the size of the epileptogenic effect might be too small or not frequent enough to detect it in the present IGE sample.
Lenzen
Kirsten P
KP
Gene Mapping Center, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Heils
Armin
A
Lorenz
Susanne
S
Hempelmann
Anne
A
Sander
Thomas
T
D017668:Age of Onset; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D018900:Dinucleotide Repeats / Q000235:genetics; D004829:Epilepsy, Generalized / Q000235:genetics*; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D005858:Germany; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D015810:Linkage Disequilibrium; D008291:Malate Dehydrogenase / Q000235:genetics*; D011110:Polymorphism, Genetic
D005819:Genetic Markers; D008291:Malate Dehydrogenase; C495394:malic enzyme 2; human