von Trotha K-T, Heun R, Schmitz S, Lütjohann D, Maier W, Kölsch H
Department of Psychiatry, Sigmund-Freud Street 25, University of Bonn, 53105 Bonn, Germany.
Neurosci Lett. 2006 Jul 24;402(3):262-6. doi: 10.1016/j.neulet.2006.04.009. Epub 2006 May 26.
Linkage analyses have identified a possible hot spot for a late-onset Alzheimer's disease (LOAD) risk gene on chromosome 10q21-22 and 10q25. It was also shown that cholesterol metabolism is involved in the pathogenic mechanisms of AD. The gene of lysosomal acid lipase (LIPA) is located next to the putative hot spot on chromosome 10. Its protein is involved in cholesterol metabolism and responsible for catalysing the hydrolysis of cholesteryl esters and triglycerides inside the lysosome. Previous publications reported controversial results on the role of LIPA polymorphisms on the risk of LOAD. We investigated two LIPA polymorphisms (rs1051338 and rs2297472) for their putative effect on the risk of LOAD in a homogenous sample of German origin. Genotypes of the investigated polymorphisms in AD patients and controls were compared. Also the effect of the LIPA gene polymorphisms on plasma cholesterol levels and 24S-hydroxycholesterol/cholesterol ratios on AD patients were investigated. None of the observed polymorphisms showed a significant influence on the risk of AD. We found that LIPA exon 2 polymorphism (rs1051338) influenced plasma 24S-hydroxycholesterol/cholesterol ratios in AD patients where carriers of the C/C allele presented with higher ratios than heterozygote carriers of the LIPA allele. Even though the biological function and gene location of LIPA on chromosome 10 suggest that LIPA might be a candidate for an AD risk gene, our results revealed that polymorphisms in LIPA did not influence the risk of AD in our study.
连锁分析已确定10号染色体上10q21 - 22和10q25区域可能是晚发性阿尔茨海默病（LOAD）风险基因的一个热点。研究还表明，胆固醇代谢参与了阿尔茨海默病的致病机制。溶酶体酸性脂肪酶（LIPA）基因位于10号染色体上的假定热点附近。其蛋白质参与胆固醇代谢，负责催化溶酶体内胆固醇酯和甘油三酯的水解。先前的出版物报道了关于LIPA多态性在LOAD风险中作用的有争议结果。我们在一个德国同源样本中研究了两种LIPA多态性（rs1051338和rs2297472）对LOAD风险的假定影响。比较了AD患者和对照中所研究多态性的基因型。还研究了LIPA基因多态性对AD患者血浆胆固醇水平和24S - 羟基胆固醇/胆固醇比值的影响。所观察到的多态性均未显示对AD风险有显著影响。我们发现LIPA外显子2多态性（rs1051338）影响AD患者的血浆24S - 羟基胆固醇/胆固醇比值，其中C/C等位基因携带者的比值高于LIPA等位基因杂合子携带者。尽管LIPA在10号染色体上的生物学功能和基因位置表明LIPA可能是AD风险基因的一个候选者，但我们的结果显示，在我们的研究中LIPA多态性并未影响AD风险。
