Genome Polymorphism And Mutations Of TARDBP In SALS

Amyotrophic lateral sclerosis (ALS) is a progressive paralytic disorder resulting from the degeneration of motor neurons in brain and spinal cord. Sporadic ALS (SALS) accounts for majority of patients. ALS is a kind of complex disorder. There were several SNPs reported to be associated with SALS in recently published articles about genome-wide association (GWA) of ALS. Transactive response DNA binding protein(TARDBP) gene mutations in ALS are responsible for about0.5%-3%of ALS cases. Mutation of TARDBP gene may be another common cause of sporadic ALS.OBJECTIVE:We study the genome polymorphism in SALS of Chinese origin; search for TRADBP mutations in SALS cases.METHODS:We recruited86individuals with SALS and94matched controls for our study, extracted genomic DNA from blood samples. Alleles were determined by a MALDI-TOF based approach followed by association analysis. The coding region of TARDBP exon6, was amplified by polymerase chain reaction (PCR). The PCR products were genotyped using high-resolution melting technology (HRM).RESULTS:1. Individual genotype data for8SNPs in Chinese population showed no significant association with SALS. On analysis of combined genotyping data, rs1942239gained in strength of allelic association.2. We observe one silent mutation (1098C>G) in2Chinese individuals with SALS. The mutation was not reported before and less likely to be pathogenic. No missense mutation is found in89Chinese individuals with SALS.CONCLUSIONS:1. Research provides new data of Asian people for ALS GWA. No SNP is definitively associated with increased risk of developing disease in Chinese population. Variants of GALNT1(near SNP rs1942239) may confer susceptibility to sporadic ALS based on the combined data.2. No TARDBP missense mutation is found in89Chinese cases. Our data indicates that genetic variation in TARDBP may be not a common cause of sporadic ALS in Chinese.