Association between the macrophage inflammatory protein-l alpha gene polymorphism and Alzheimer's disease in the Chinese population.
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.
Li
Keshen
K
Department of Biomedical Engineering, Harbin Engineering University, Harbin 150001, China.
Dai
Dawei
D
Yao
Lifen
L
Gu
Xuefeng
X
Luan
Kuan
K
Tian
Wenjing
W
Zhao
Yashuang
Y
Wang
Binyou
B
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*
D053327:Apolipoprotein E4; C515429:CCL3 protein, human; D054405:Chemokine CCL3