title: Genetic analysis of tumor necrosis factor-alpha (TNF-alpha) G-308A and Saitohin Q7R polymorphisms with Alzheimer's disease.
abstract: Neuroinflammation 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 epsilon4) status, increased LOAD risks associated with the AA genotype and A-allele only in the APOE epsilon4 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-alpha gene G-308A polymorphism might be a risk factor for LOAD and dependent on APOE epsilon4 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.
authors.affiliation: National Research Institute for Family Planning, Beijing, 100081 China.
authors.forename: Binbin
authors.initials: B
authors.lastname: Wang
authors.forename: Sirui
authors.initials: S
authors.lastname: Zhou
authors.forename: Ze
authors.initials: Z
authors.lastname: Yang
authors.forename: Yan-Chen
authors.initials: YC
authors.lastname: Xie
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.forename: Zeping
authors.initials: Z
authors.lastname: Lv
authors.forename: Chenguang
authors.initials: C
authors.lastname: Zheng
authors.forename: Xu
authors.initials: X
authors.lastname: Ma
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics; D001120:Arginine / Q000235:genetics*; D016009:Chi-Square Distribution; D002681:China / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D005973:Glutamine / Q000235:genetics*; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D016875:tau Proteins / Q000235:genetics*
chemical_list: D053327:Apolipoprotein E4; C458340:STH protein, human; D014409:Tumor Necrosis Factor-alpha; D016875:tau Proteins; D005973:Glutamine; D001120:Arginine