Periyasamy Sabapathy, Sathya Mohan, Karthick Chennakesavan, Kandasamy Mahesh, Shanmugaapriya Sellathamby, Tamilselvan Jeyavelu, Jayachandran Kesavan Swaminathan, Anusuyadevi Muthuswamy
Department of Biochemistry, Molecular Gerontology Laboratory, Bharathidasan University, Tiruchirappalli, India.
UGC-Faculty Recharge Program (UGC-FRP), University Grant Commission, Laboratory of Stem cells and Neuroregeneration, Department of Animal Science, Bharathidasan University, Tiruchirappalli, Tamilnadu, India.
J Alzheimers Dis. 2017;60(s1):S195-S207. doi: 10.3233/JAD-170272.
Epidemiological studies state that dementia has multiple etiologies including genetic mutation, genetic variation, and environmental factors. Accumulating evidence suggests that dysregulation of cholesterol homeostasis is the major etiological factor in initiating neurodegeneration. Apolipoprotein E (APOE) polymorphic alleles and associated polymorphism of lipoprotein lipase (LPL) and cholesteryl ester transfer protein (CETP) that are important components in regulating cholesterol metabolism are implicated in neurodegenerative diseases. Therefore, the current study focused on identifying the association between several common polymorphism (viz., APOE, CETP, and LPL) to that of change in serum lipid levels and memory symptoms. Volunteer subjects aged 50 and above from rural and tribal areas of the Dharmapuri district, Tamilnadu, India were chosen for the current study and polymorphism was analyzed using PCR-RFLP. Fasting lipid profile and memory function using simplified version of Global Clinical Dementia rating were assessed. Significant difference in the major lipid profile parameters were observed (TC, TGL, LDL, VLDL) among rural and tribal populations that were associated with significant genotypic variation of APOE, CETP, and LPL. Regression analysis revealed significant risk for memory loss that are dependent on age and genetic variants like CETP. These data predict positive correlation between cholesterol-associated genes and their relationship to altered lipid profile and memory symptoms, which possibly link gene-polymorphism and susceptibility ratio for aging and dementia.
流行病学研究表明，痴呆症有多种病因，包括基因突变、基因变异和环境因素。越来越多的证据表明，胆固醇稳态失调是引发神经退行性变的主要病因。载脂蛋白E（APOE）多态性等位基因以及脂蛋白脂肪酶（LPL）和胆固醇酯转运蛋白（CETP）的相关多态性，这些是调节胆固醇代谢的重要组成部分，与神经退行性疾病有关。因此，本研究重点在于确定几种常见多态性（即APOE、CETP和LPL）与血脂水平变化和记忆症状之间的关联。本研究选取了印度泰米尔纳德邦达摩布里区农村和部落地区50岁及以上的志愿者作为研究对象，并采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析多态性。使用简化版的全球临床痴呆评定量表评估空腹血脂谱和记忆功能。在农村和部落人群中观察到主要血脂谱参数（总胆固醇、甘油三酯、低密度脂蛋白、极低密度脂蛋白）存在显著差异，这与APOE、CETP和LPL的显著基因型变异有关。回归分析显示，记忆丧失的显著风险取决于年龄和CETP等基因变异。这些数据预测了胆固醇相关基因之间的正相关及其与血脂谱改变和记忆症状的关系，这可能将基因多态性与衰老和痴呆的易感性联系起来。
