MAPT as a predisposing gene for sporadic amyotrophic lateral sclerosis in the Chinese Han population

• 作 者: Pu Fang Wenyuan Xu Chengsi Wu Min Zhu Xiaobing Li Daojun Hong
• 机 构: Department of Neurology,the First Affiliated Hospital of Nanchang University,
• 出 处: Neural Regeneration Research
• 发表日期: 2013年33期
• 关键词: neural regeneration sporadic amyotrophic lateral sclerosis microtubule-associate

A previous study of European Caucasian patients with sporadic amyotrophic lateral sclerosis demonstrated that a polymorphism in the microtubule-associated protein Tau(MAPT) gene was significantly associated with sporadic amyotrophic lateral sclerosis pathogenesis.Here,we tested this association in 107 sporadic amyotrophic lateral sclerosis patients and 100 healthy controls from the Chinese Han population.We screened the mutation-susceptible regions of MAPT–the 3′ and 5′ untranslated regions as well as introns 9,10,11,and 12–by direct sequencing,and identified 33 genetic variations.Two of these,105788 A>G in intron 9 and 123972 T>A in intron 11,were not present in the control group.The age of onset in patients with the 105788 A>G and/or the 123972 T>A variant was younger than that in patients without either genetic variation.Moreover,the patients with a genetic variation were more prone to bulbar palsy and breathing difficulties than those with the wild-type genotype.This led to a shorter survival period in patients with a MAPT genetic variant.Our study suggests that the MAPT gene is a potential risk gene for sporadic amyotrophic lateral sclerosis in the Chinese Han population.

A previous study of European Caucasian patients with sporadic amyotrophic lateral sclerosis prototype that a polymorphism in the microtubule-associated protein Tau (MAPT) gene was significantly associated with sporadic amyotrophic lateral sclerosis pathogenesis. Here, we tested this association in 107 sporadic amyotrophic lateral sclerosis patients and 100 healthy controls from the Han population. We screened the mutation-susceptible regions of MAPT-the 3 ’and 5’ untranslated regions as well as introns 9, 10, 11, and 12-by direct sequencing, and identified 33 genetic variations . Two of these, 105788 A> G intron 9 and 123972 T> A intron 11, were not present in the control group. The age of onset in patients with the 105788 A> G and / or the 123972 T> A variant was younger than that in patients without either genetic variation. More than that, the patients with a genetic variation were more prone to bulbar palsy and breathing difficult than those with the wild-type genotype. This led to a shorter survival period in patients with a MAPT genetic variant. Our study suggests that the MAPT gene is a potential risk gene for sporadic amyotrophic lateral sclerosis in the Chinese Han population.