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-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.