Association between selected cholesterol-related gene polymorphisms and Alzheimer’s disease in a Turkish cohort
Numerous genetic evidence has pointed out that variations in cholesterol-related genes may be associated with an Alzheimer’s disease (AD) risk. We aimed to investigate the association between polymorphisms in several cholesterol-related genes [APOA5 (rs662799), APOC1 (rs11568822), APOD (rs1568565), CH25H (rs13500), LDLR (rs5930), SORL1 (rs2282649)] and AD in a cohort of Turkish patients. The study group consisted of 257 AD patients (mean age: 75.9 years ± 10.4) and 414 controls (mean age: 62.2 years ± 13.1). Genotyping was performed by quantitative real-time polymerase chain reaction using hydrolysis probes. Our results showed that the ‘TT’ genotype of CH25H rs13500 polymorphism was significantly more frequent in the AD group (p < 0.001) and individuals carrying the CH25H ‘T’ allele had an increased risk for AD (OR 3.07, 95% CI 2.13–4.44, p = 2.20e−09) independently from age, gender and APOE ε4 allele. Moreover, this risk was excessively increased (OR 14.04, 95% CI 6.99–28.23, p = 9.78e−14) in the presence of APOE ε4 allele. The ‘ins/ins’ genotype of APOC1 rs11568822 was significantly more frequent in the AD group compared to controls (p = 1.95e−08). However, this increased AD risk in ‘ins/ins’ carriers was found to be dependent on their APOE ε4 carrier status. No significant associations were found in allele and genotype distributions of APOA5, APOD, LDLR and SORL1 gene polymorphisms. Our results suggest that the association between APOC1 ‘ins/ins’ genotype and AD risk can be explained by linkage disequilibrium with the APOE locus. CH25H rs13500 polymorphism is associated with an AD risk in the Turkish population and CH25H might have a role in the pathogenesis of AD together with, and independently from APOE.
KeywordsAlzheimer’s disease Cholesterol metabolism Polymorphism Risk
The authors thank all the patients and their families. Meltem Pak helped with obtaining the samples. This work was supported by the Research Fund of Istanbul University (Project No: TAB-2017-23218).
Compliance with ethical standards
Conflict of interest
The authors have no actual or potential conflicts of interest.
- 7.Gopalraj RK, Zhu H, Kelly JF, Mendiondo M, Pulliam JF, Bennett DA, Estus S (2005) Genetic association of low density lipoprotein receptor and Alzheimer’s disease. Neurobiol Aging 26:1–7. https://doi.org/10.1016/j.neurobiolaging.2004.09.001 CrossRefGoogle Scholar
- 14.McKhann GM et al (2011) The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7:263–269. https://doi.org/10.1016/j.jalz.2011.03.005 CrossRefGoogle Scholar
- 16.Nilsson SK, Heeren J, Olivecrona G, Merkel M (2011) Apolipoprotein A-V: a potent triglyceride reducer. Atherosclerosis 219:15–21. https://doi.org/10.1016/j.atherosclerosis.2011.07.019 CrossRefGoogle Scholar
- 19.Pappolla MA et al (2003) Mild hypercholesterolemia is an early risk factor for the development of Alzheimer amyloid pathology. Neurology 61:199–205 doi. https://doi.org/10.1212/01.Wnl.0000070182.02537.84 CrossRefGoogle Scholar
- 21.Picard C et al (2018) Alterations in cholesterol metabolism-related genes in sporadic Alzheimer’s disease. Neurobiol Aging 66:180e181–180e189 https://doi.org/10.1016/j.neurobiolaging.2018.01.018 CrossRefGoogle Scholar
- 27.Riemenschneider M et al (2004) Association analysis of genes involved in cholesterol metabolism located within the linkage region on chromosome 10 and Alzheimer’s disease. Neurobiol Aging 25:1305–1308. https://doi.org/10.1016/j.neurobiolaging.2004.01.001 CrossRefGoogle Scholar
- 28.Rodriguez E, Mateo I, Llorca J, Sanchez-Quintana C, Infante J, Berciano J, Combarros O (2006) Brief research communication - No association between low density lipoprotein receptor genetic variants and Alzheimer’s disease risk. Am J Med Genet B 141B:541–543. https://doi.org/10.1002/ajmg.b.30341 CrossRefGoogle Scholar
- 36.Xu C, Bai R, Zhang D, Li Z, Zhu H, Lai M, Zhu Y (2013) Effects of APOA5 −1131T>C (rs662799) on fasting plasma lipids and risk of metabolic syndrome: evidence from a case-control study in China and a meta-analysis. PLoS ONE 8:e56216. https://doi.org/10.1371/journal.pone.0056216 CrossRefGoogle Scholar