title: Association between the macrophage inflammatory protein-l alpha gene polymorphism and Alzheimer's disease in the Chinese population.
abstract: 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-1alpha) 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-1alpha gene promoter region at position -906. We investigated whether this promoter polymorphism of MIP-1alpha 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-1alpha and apolipoprotein E (APOE) genes. The overall distribution of MIP-1alpha-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 varepsilon4 and MIP-1alpha (TA)(6)/(TA)(6) carriers was 7.140 (95% CI=3.222-15.823). In addition, we found that serum MIP-1alpha 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-1alpha-906 (TA)(6)/(TA)(6) genotype, either by itself or interacting with the APOE varepsilon4 gene seems to be a genetic risk factor for AD. This genotype is associated with elevated serum MIP-1alpha levels in patients, which can contribute to increase the inflammatory process occurring in AD.
authors.affiliation: Department of Biomedical Engineering, Harbin Engineering University, Harbin 150001, China.
authors.forename: Keshen
authors.initials: K
authors.lastname: Li
authors.forename: Dawei
authors.initials: D
authors.lastname: Dai
authors.forename: Lifen
authors.initials: L
authors.lastname: Yao
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Gu
authors.forename: Kuan
authors.initials: K
authors.lastname: Luan
authors.forename: Wenjing
authors.initials: W
authors.lastname: Tian
authors.forename: Yashuang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Binyou
authors.initials: B
authors.lastname: Wang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics; D044466:Asian People / Q000208:ethnology; D016022:Case-Control Studies; D054405:Chemokine CCL3 / Q000097:blood / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*
chemical_list: D053327:Apolipoprotein E4; C515429:CCL3 protein, human; D054405:Chemokine CCL3