Association between the macrophage inflammatory protein-l alpha gene polymorphism and Alzheimer's disease in the Chinese population

• Published in: Neuroscience letters 2008-03, Vol.433 (2), p.125-128
• Main Authors: Li, Keshen, Dai, Dawei, Yao, Lifen, Gu, Xuefeng, Luan, Kuan, Tian, Wenjing, Zhao, Yashuang, Wang, Binyou
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - blood; Alzheimer Disease - ethnology; Alzheimer Disease - genetics; Alzheimer's disease; Apolipoprotein E4 - genetics; Asian Continental Ancestry Group - ethnology; Association study; Case-Control Studies; Chemokine CCL3 - blood; Chemokine CCL3 - genetics; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Macrophage inflammatory protein-l alpha gene; Male; Middle Aged; Polymorphism, Genetic - genetics; Promoter polymorphism; Risk factor
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2008.01.002

Genetic polymorphisms in chemokine receptor and their natural ligand genes have been shown to modify the disease progression of Alzheimer's disease (AD). Human macrophage inflammatory protein-1 alpha (MIP-1α) is a chemotactic cytokine which plays a considerable role in AD pathogenesis, but its genetic contribution to AD has never been investigated. Recently, a biallelic dinucleotide microsatellite repeat (TA repeat) polymorphism has been found in the MIP-1α gene promoter region at position -906. We investigated whether this promoter polymorphism of MIP-1α gene might be responsible for susceptibility to AD in a Chinese population, utilizing a clinically well-defined group of 138 sporadic AD patients and 180 age-matched controls. We also examined the combined gene effects between the MIP-1α and apolipoprotein E (APOE) genes. The overall distribution of MIP-1α-906 alleles and genotypes was significantly different between AD cases and controls ( P < 0.05). The odds ratio for AD associated with the (TA) 6/(TA) 6 versus non-(TA) 6/(TA) 6 genotype was 1.893 (95% CI = 1.208–2.967), while that for APOE ɛ4 and MIP-1α (TA) 6/(TA) 6 carriers was 7.140 (95% CI = 3.222–15.823). In addition, we found that serum MIP-1α levels in patients with (TA) 6/(TA) 6 genotype were increased significantly when compared with non-(TA) 6/(TA) 6 genotype. The results indicate that the MIP-1α-906 (TA) 6/(TA) 6 genotype, either by itself or interacting with the APOE ɛ4 gene seems to be a genetic risk factor for AD. This genotype is associated with elevated serum MIP-1α levels in patients, which can contribute to increase the inflammatory process occurring in AD.