Bertram L, Guénette S, Jones J, Keeney D, Mullin K, Crystal A, Basu S, Yhu S, Deng A, Rebeck G W, Hyman B T, Go R, McInnis M, Blacker D, Tanzi R
Genetics and Aging Unit, Massachusetts General Hospital, Harvard Medical School, Charlestown, USA.
Ann Neurol. 2001 Jan;49(1):114-6. doi: 10.1002/1531-8249(200101)49:1<114::aid-ana18>3.0.co;2-m.
Two recent case-control studies have suggested a strong association of a missense polymorphism in exon 2 of the cathepsin D gene (CTSD) and Alzheimer disease (AD). However, these findings were not confirmed in another independent study. We analyzed this polymorphism in two large and independent AD study populations and did not detect an association between CTSD and AD. The first sample was family-based and included 436 subjects from 134 sibships discordant for AD that were analyzed using the sibship disequilibrium test (SDT, p = 0.68) and the sib transmission/disequilibrium test (Sib-TDT, p = 0.81). The second sample of 200 AD cases and 182 cognitively normal controls also failed to show significant differences in the allele or genotype distribution in cases versus controls (chi2, p = 0.91 and p = 0.88, respectively). In addition, two-point linkage analyses in an enlarged family sample (n = 670) did not show evidence for linkage of the chromosomal region around CTSD. Thus, our analyses on more than 800 subjects suggest that if an association between the CTSD exon 2 polymorphism and AD exists, it is likely to be smaller than previously reported.
最近的两项病例对照研究表明，组织蛋白酶D基因（CTSD）外显子2中的错义多态性与阿尔茨海默病（AD）之间存在强烈关联。然而，这些发现并未在另一项独立研究中得到证实。我们在两个大型独立的AD研究人群中分析了这种多态性，未发现CTSD与AD之间存在关联。第一个样本基于家庭，包括来自134个AD不一致同胞对的436名受试者，使用同胞对不平衡检验（SDT，p = 0.68）和同胞传递/不平衡检验（Sib-TDT，p = 0.81）进行分析。第二个样本包括200例AD病例和182名认知正常对照，病例与对照之间的等位基因或基因型分布也未显示出显著差异（卡方检验，p分别为0.91和0.88）。此外，在一个扩大的家庭样本（n = 670）中进行的两点连锁分析未显示CTSD周围染色体区域存在连锁的证据。因此，我们对800多名受试者的分析表明，如果CTSD外显子2多态性与AD之间存在关联，其关联程度可能比之前报道的要小。
