Bao Jie, Wang Xiao-jie, Mao Zong-fu
Global Health Institute, Wuhan University, Wuhan, Hubei, China (mainland).
Wuhan Women and Children Medical Care Center, Wuhan, Hubei, China (mainland).
Med Sci Monit. 2016 Jan 22;22:234-43. doi: 10.12659/msm.895622.
Alzheimer disease (AD) has become an epidemic within the growing elderly population and effective therapies of AD have not been discovered. Genetic factors accounted for over 70% of the incidence of AD and the disease-related polymorphisms are located on chromosome 19, which is one of several prominent chromosomes related to the development of AD. Many inconsistent associations between polymorphisms in ABCA7, CD33, and TOMM40 genes and the susceptibility to AD have been suggested by several independent studies.
MATERIAL/METHODS: A comprehensive literature search for studies involving the association between gene polymorphisms and AD was performed, and we finally selected 3 genes (4 polymorphisms) for the meta-analysis: ABCA7 (rs3764650), CD33 (rs3865444), and TOMM40 (rs157580, rs2075650).
A total of 25 articles investigating 3 genes (4 polymorphisms) were included in the meta-analysis. The pooled results of 4 polymorphisms were all significantly associated with the susceptibility to AD. The pooled effect of ABCA7 rs3764605 allele G was significantly associated with an increased the risk of AD (OR=1.20, 95% CI: 1.14-1.26, P value <0.001). Similarly, our evidence suggested that allele A of TOMM40 rs2075650 polymorphism was a risk factor for AD (OR=2.87, 95% CI: 2.46-3.34, P value <0.001). Alleles A of CD33 rs3865444 and A of TOMM40 rs157580 were both protective factors for AD onset (OR=0.94, 95% CI: 0.90-0.98, P value=0.003; OR=0.62, 95% CI: 0.57-0.66, P value <0.001). CONCLUSIONS" Results from the meta-analysis revealed that the pooled ABCA7 rs376465, CD33 rs3865444, TOMM40 rs157580, and rs2075650 variants were significantly associated with the susceptibility to AD. However, the association differed significantly between Asian and Caucasian groups for SNPs of CD33 rs3865444, TOMM40 rs157580, and rs2075650.
阿尔茨海默病（AD）在不断增长的老年人口中已成为一种流行病，且尚未发现有效的AD治疗方法。遗传因素占AD发病率的70%以上，与该疾病相关的多态性位于19号染色体上，19号染色体是与AD发展相关的几个重要染色体之一。多项独立研究表明，ABCA7、CD33和TOMM40基因的多态性与AD易感性之间存在许多不一致的关联。
材料/方法：对涉及基因多态性与AD关联的研究进行全面文献检索，最终选择3个基因（4个多态性位点）进行荟萃分析：ABCA7（rs3764650）、CD33（rs3865444）和TOMM40（rs157580、rs2075650）。
荟萃分析共纳入25篇研究3个基因（4个多态性位点）的文章。4个多态性位点的合并结果均与AD易感性显著相关。ABCA7 rs3764605位点的G等位基因合并效应与AD风险增加显著相关（OR=1.20，95%CI：1.14 - 1.26，P值<0.001）。同样，我们的证据表明，TOMM40 rs2075650多态性的A等位基因是AD的一个风险因素（OR=2.87，95%CI：2.46 - 3.34，P值<0.001）。CD33 rs3865444的A等位基因和TOMM40 rs157580的A等位基因均为AD发病的保护因素（OR=0.94，95%CI：0.90 - 0.98，P值=0.003；OR=0.62，95%CI：0.57 - 0.66，P值<0.001）。结论：荟萃分析结果显示，ABCA7 rs376465、CD33 rs3865444、TOMM40 rs157580和rs2075650的合并变异与AD易感性显著相关。然而，对于CD33 rs3865444、TOMM40 rs157580和rs2075650的单核苷酸多态性，亚洲人和白种人群之间的关联存在显著差异。
