The Study Of The Association Of SNPs Of The CLCN2 Gene With Idiopathic Generalized Tonic-clonic Seizures In The Six Minority Ethnic Isolated People And Han People From Yunnan Province

Background and objectHeterozygous mutations in the CLCN2 gene encoding the voltage-gated chloride channel CLC2 have been identified in patients with idiopathic generalized tonic-colonic seizures (IGTCS). To investigate the involvement of CLCN2 in the six minority ethnic isolated people(Achang people, Deang people, Nu people, Bulang People, Wa People, Lahu people, Jinuo People)and Han people from Yunnan province.M ateri als and methodsCollecting 59 I GTCS patients of the six minority ethnic isolated people and part of their family members(18 pati ents with I GTCS of Hani people and 18 their rel ati ves,4 Patients with I GTCS of Buyi people and 4 their relatives,9 patients with I GTCS of Yi people and 3 their relatives13 patients with IGTCS of Nu people and 10 their relatives,6 pati ents with I GTCS of Deang people and 5 their relatives,9 patients with IGTCS of Achang people and 9 their relatives) and 149 patients of Han people with IGTCS with the subjects of the control group were 83 Han people eliminated EPs by clinical examination. We examined single-nucleotide polymorphisms (SNPs) of CLCN2 in attempting to examine whether SNPs or heliotype molecular markers would confer a significant susceptibility to IGTCS. The SNPs (rs13099401,rs9820376,rs6773786,rs4912540,rs67708085) present in the gene CLCN2 were analyzed by Multiplex Snapshot method. We carry out the polymorphism screening for genetic CLCN2 association between SNPs and phenotypes in xxx IGTCS patients and in xxx healthy subjects, and then to validate the initial finds resulting from the case-control study to determine weather the SNPs or haplotype is associated with IGTCS in the six minority ethnic isolated people and Han people from Yunnan province.Result:We completed an association analysis with five SNPs(rs13099401,rs9820376,rs6773786,rs4912540,rs6770808) located wi thi n the CL CN2 gene using the case control association tests, the results showed that the genotype and allele frequency in rs13099401,rs9820376,rs6773786, rs4912540 were found not different between IGTCS patients and control subjects(P＞0.05). While for the rs6770808, the result showed that the distribution of the three genotypes, TT,TC and CC, has a significant difference between the Han patients with IGTCS and the normal controls(χ2=7.385, P=0.025). the frequency of the three genotypes has a significant difference between the normal controls of Han people and patients with IGTCS in Han people (χ2=7.137, P=0.008). Distribution of the three genotypes has no significant difference between the normal controls of the Han people with IGTCS and patients with IGTCS in the minority ethnic isolated people(x2=1.139, P=0.566), the frequency of C allele in rs6770808 were significantly higher in control subjects than IGTCS patients (P< 0.05); Distribution of the TT and non-TT gene type, and TC and non-TC gene type has a significant difference between the Han people with IGTCS and the their normal controls.Conclusion:1.our preliminary results provide evidence that the rs6770808 of CLCN2 gene may be important risk factors for the development of IGTCS in the population of six minority ethnic isolated people(Hani People, Buyi People, Yi People, Nu People, Deang People, Achang people)and Han people from Yunnan province.2.our results do not support the association between these SNPs(rs13099401,rs9820376,rs6773786,rs4912540) of CLCN2 gene and IGTCS susceptibility in the population. The results suggest that haplotype composed of alleles of these SNPs of CLCN2 gene do not contribute significantly to the predisposition to develop IGTCS in our population.3. our results suggest that there is no significant difference between the two group in the SNP(rs6770808) of CLCN2 gene in different population.4.our results suggest that the SNP rs6770808 may be a potential susceptible polymorphism causing idiopathic generalized tonic-clonic seizures. The CC gene type play a protect rol e i n the I GTCS patients, however, the gene type TT i ncrease the ri sk of IGTCS. Key words:minority ethnic; idiopathic general i zed toni c-clonic seizures; genetics;...