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

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-α ( TNF-α ) encoding TNF-α 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 ( χ 2 = 8.74, df = 1, P = 0.0031, and χ 2 = 4.47, df = 1, P = 0.035) were found. After stratifying by apolipoprotein E allele 4 ( APOE e4 ) status, increased LOAD risks associated with the AA genotype and A-allele only in the APOE e4 non-carriers ( χ 2 = 9.21, df = 1, P = 0.002; χ 2 = 10.02, df = 1, P = 0.0015) were seen. These results suggested that the TNF-α gene G-308A polymorphism might be a risk factor for LOAD and dependent on APOE e4 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.