Genetic analysis of tumor necrosis factor-α (TNF-α) G-308A and Saitohin Q7R polymorphisms with Alzheimer's disease

作者：Wang, Binbin; Zhou, Sirui; Yang, Ze^*; Xie, Yan-Chen; Wang, Jing; Zhang, Peng; Lv, Zeping; Zheng, Chenguang; Ma, Xu

来源：Journal of the Neurological Sciences, 2008, 270(1-2): 148-151.

DOI：10.1016/j.jns.2008.02.021

• late-onset Alzheimer's disease
• APOE epsilon 4
• TNF-alpha
• STH
• case-control study
• Chinese

Neuro inflammation and abnormal phosphorylation of TAU proteins have been implicated in the etiology of Alzheimer's disease (AD). Several studies have suggested the G-308A promoter polymorphism in one of the proinflammatory cytokine genes tumor necrosis factor-alpha (TNF-alpha) encoding TNF-alpha may be associated with AD pathogenesis. Association between the Q7R polymorphism in saitohin (STH), a gene nested within the intron of the Tau gene, has also been reported. @@@ To determine whether these two polymorphisms contribute to the risk for late-onset AD (LOAD) in Chinese, we have investigated 207 sporadic LOAD patients and 222 healthy controls. @@@ The associations of the AA genotype and A-allele with LOAD (chi(2) = 8.74, df = 1, P = 0.0031, and chi(2) = 4.47, df = 1, P = 0.035) were found. After stratifying by apolipoprotein E allele 4 (APOE epsilon 4) status, increased LOAD risks associated with the AA genotype and A-allele only in the APOE e4 non-carriers (chi(2) = 9.21, df = 1, P = 0.002; chi(2) = 10.02, df= 1, P = 0.0015) were seen. These results suggested that the TNF-a gene G-308A polymorphism might be a risk factor for LOAD and dependent on APOE epsilon 4 status in Chinese. @@@ Homozygous Q/Q of STH Q7R polymorphism was the only one genotype found in either LOAD group or controls. No R allele was detected in LOAD and control groups. The extremely rare frequency of the ancestral R allele differs sharply from that observed in studies in the Caucasian population, suggesting obvious ethnic differences.

• 出版日期2008-7-15
• 单位北京医院; 广西壮族自治区江滨医院; 首都医科大学; 中国医学科学院北京协和医院; 国家卫生计生委科学技术研究所