Association of a haplotype for tumor necrosis factor in siblings with late-onset Alzheimer disease: The NIMH Alzheimer disease genetics initiative

✍ Scribed by Collins, Julianne S. ;Perry, Rodney T. ;Watson, Bracie ;Harrell, Lindy E. ;Acton, Ronald T. ;Blacker, Deborah ;Albert, Marilyn S. ;Tanzi, Rudolph E. ;Bassett, Susan S. ;McInnis, Melvin G. ;Campbell, R. Duncan ;Go, Rodney C.P.

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 120 KB
• Volume: 96
• Category: Article
• ISSN: 0148-7299
• DOI: 10.1002/1096-8628(20001204)96:6<823::aid-ajmg26>3.0.co;2-i

✦ Synopsis

Tumor necrosis factor (TNF), a proinflammatory cytokine, may be involved in the pathogenesis of Alzheimer disease (AD) based on observations that senile plaques have been found to upregulate proinflammatory cytokines. Additionally, nonsteroidal anti-inflammatory drugs have been found to delay and prevent the onset of AD. A collaborative genome-wide scan for AD genes in 266 late-onset families implicated a 20 centimorgan region at chromosome 6p21.3 that includes the TNF gene. Three TNF polymorphisms, a -308 TNF promoter polymorphism, whose TNF2 allele is associated with autoimmune inflammatory diseases and strong transcriptional activity, the -238 TNF promoter polymorphism, and the microsatellite TNFa, whose 2 allele is associated with a high TNF secretion, were typed in 145 families consisting of 562 affected and unaffected siblings. These polymorphisms formed a haplotype, 2-1-2, respectively, that was significantly associated with AD (P = 0.005) using the sibling disequilibrium test. Singly, the TNFa2 allele was also significantly associated (P = 0.04) with AD in these 145 families. This TNF association with AD lends further support for an inflammatory process in the pathogenesis of AD.