An α-2-macroglobulin insertion-deletion polymorphism in alzheimer disease

摘要: Blacker et al.1 reported an association between Alzheimer disease (AD) and the deletion allele (A2M*2) of intronic polymorphism in -2-macroglobulin gene (A2M; 2), which confers a risk for AD (OR=3.55, 95% CI=1.90-7.03) comparable with that APOE*E4 (OR=3.54, CI=1.76-7.12). We analysed two independent sets families3, 4 using same family-based (sibship disequilibrium test1 (SDT) sib transmission-disequilibrium test5 (S-TDT)) methods. Following scheme al.1, we limited these analyses to nuclear families European descent all affected individuals had onset over 50 years, marker information was available at least one unaffected and, case S-TDT, or more distinct genotypes were present sibship. averaged P values S-TDT 100 iterations (10,000 replicates per iteration) Monte-Carlo method6. Both data demonstrated (SDT, Duke, P=0.000007; Toronto, P=0.0009), indicating sufficient power detect associations magnitude A2M*2 (1). Although prior evidence shows pedigrees are enriched locus on chromosome 12 near A2M (Refs 3,7), unable either SDT even when "stringent unaffecteds" method1 applied n = 60, 0.80, 45, 0.82; 17, 0.64, 21, 0.75). Furthermore, did not series sporadic cases after adjustment status (Table 1), despite fact each set than 80% odds ratio as low 1.87 (an effect much smaller A2M*2; 1).