Lin P I, Martin E R, Bronson P G, Browning-Large C, Small G W, Schmechel D E, Welsh-Bohmer K A, Haines J L, Gilbert J R, Pericak-Vance M A
Center for Human Genetics, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Neurology. 2006 Jul 11;67(1):64-8. doi: 10.1212/01.wnl.0000223438.90113.4e.
Previous linkage studies have shown that chromosome 12 harbors susceptibility genes for late-onset Alzheimer disease (LOAD). However, association studies of several candidate genes on this chromosome region have produced ambiguous results. A recent study reported the association between the glyceraldehyde-3-phosphate dehydrogenase (GAPD) gene on chromosome 12p and the risk of LOAD.
The authors conducted family-based and case-control association studies in two independent LOAD data sets on 12 single-nucleotide polymorphisms (SNPs) in the GAPD gene and its paralogs.
No association was found of the GAPD gene with LOAD in the family-based data set, but marginal evidence of association was seen in the later-onset subgroup when age at onset was stratified. The SNP rs2029721 in one GAPD pseudogene was also found to be associated with risk for LOAD in the unrelated case-control data set (p = 0.003).
The GAPD gene and its pseudogene may play a role in the development of late-onset Alzheimer disease. However, the effect, if any, is likely to be limited.
先前的连锁研究表明，12号染色体携带着晚发性阿尔茨海默病（LOAD）的易感基因。然而，对该染色体区域几个候选基因的关联研究结果并不明确。最近一项研究报道了12号染色体短臂上的甘油醛-3-磷酸脱氢酶（GAPD）基因与LOAD风险之间的关联。
作者在两个独立的LOAD数据集中，对GAPD基因及其旁系同源基因中的12个单核苷酸多态性（SNP）进行了基于家系的和病例对照的关联研究。
在基于家系的数据集中未发现GAPD基因与LOAD有关联，但在按发病年龄分层的晚发亚组中发现了微弱的关联证据。在无关的病例对照数据集中，还发现一个GAPD假基因中的SNP rs2029721与LOAD风险相关（p = 0.003）。
GAPD基因及其假基因可能在晚发性阿尔茨海默病的发生发展中起作用。然而，即便有作用，其影响可能也很有限。
