POSTER NO: 410

Association study and candidate gene study of Childhood absence epilepsy in north Chinese people

¹Yucai Chen, ¹Jianjun Lv, ¹Hong Pan, ¹Yuehua Zhang, ¹Yuwu Jiang, ²Keyue Ding, ²Yan Shen, ¹Xiru Wu
¹Pediatric Department, the First Hospital, Peking University, Beijing 100034, P.R. China., ²National Center of Human Genome Research, Beijing 100176, P.R. China.

Childhood absence epilepsy (CAE), one of the common idiopathic generalized epilepsies, accounts for 8 to 15% of all childhood epilepsies. Frequent absence attacks start in early or mid childhood and disappear by 30 years of age or may persist through life. At least four phenotypic subcategories of CAE have been proposed. A subtype persisting with tonic clonic seizures has been mapped to 8q24 , between D8S554 and D8S502. To investigate whether or not the childhood absence epilepsy (absence seizures as the sole phenotype) in North Chinese people is linkaged to Chromosome 8q24, we designed this study program. First of all, five microsatellite DNA D8S1783, D8S1753, D8S1717, D8S554 and D8S274 adjoining to chromosome 8q24 are used as genetic markers. Both case-control study and fluorescence-based semi-automated genotyping technique were used in 90 CAE patients who have absence epilepsy as sole phenotype and 100 controls of North China to conduct association analysis. In Chinese normal population, the allele frequencies of the 5 microsatellite DNA are in good agreement with Hardy-Weinberg equilibrium. Selected microsatellite DNA are good genetic markers that can be used in linkage and association study in Chinese people. The frequency of some alleles of the 3 microsatellite DNA showed significant discrepancy between CAE patients and normal controls, such as D8S554*5 allele (chi-square=10.658, df=1, p<0.001), D8S554*6 allele (chi-square=8.495, df=1, p<0.001), D8S554*7 allele (chi-square=11.294, df=1, p<0.001), D8s1783*5 (chi-square=4.573, df=1, p<0.001), D8s1753*13allele (chi-square=3.942, df=1, p<0.050), D8S1753*15 allele (chi-square=6.7688, df=1, p<0.05). Transmission/disequilibrium test (TDT), in addition to fluorescence-based semi-automated genotyping technique were used in 91 CAE trios with absence epilepsy as sole phenotype in North Chinese people. 91 nuclear families with at least one CAE patients are studied. The above five microsatellites were also used in this study. The result showed some signs of transmission disequilbrium among some alleles of D8S1783, D8S274, D8S1753, such as D8S274*4 allele, 25 of 40 alleles are not transmitted (x2=4.455, df=1, p<0.05), D8S1783*3 allele, 11 of 13 alleles are not transmitted(x2=6.23, df=1, p<0.05), D8S1753*9 allele, 18of 24 alleles are not transmitted (x2=6, df=1, p<0.05). Our study suggested that absence seizures as the sole phenotype of CAE in North Chinese people is possibly linkaged to chromosome 8q24. By e-PCR and searching against human genome project working draft databases information at UCSC, we found that T-STAR gene is located between D8S554 and D8S274. We suspected that the T-STAR gene could be involved in the pathogenesis of childhood absence epilepsy. The reasons are as follows: (1) it is located between the D8S554 and D8S274, (2) it is expressed in brain, (3) it is a novel member of signal transduction and activation of RNA family. Using direct sequencing of coding region of T-STAR gene in 48 patients and 48 normal controls, we found no mutations in patients. But we found three novel SNPs in this gene, but did not find any difference between two groups. We demonstrated that T-STAR is not involved in the pathogenesis of CAE, but cannot exclude it as a candidate gene. The reason is that we still did not study its control region.