Microsatellite polymorphisms in the gene promoter of monocyte chemotactic protein-3 and analysis of the association between monocyte chemotactic protein-3 alleles and multiple sclerosis development.
Monocyte chemotactic protein 3 (MCP-3) is a chemokine that attracts mononuclear cells, including monocytes and lymphocytes, the inflammatory cell types that predominate in multiple sclerosis lesions. We studied the possible association between the presence of a CA/GA microsatellite repeat polymorphism in the promoter/enhancer region of the MCP-3 gene and the occurrence of multiple sclerosis. DNA samples from 192 Swedish multiple sclerosis (MS) patients and 129 healthy controls were analysed by an automated fluorescent technique. In the whole sample population, five MCP-3 allele variants (MCP-3*A1 to MCP-3*A5) were detected with an allele frequency ranging between 0.3% and 46%. The individual MCP-3 allele frequencies did not differ significantly between MS patients and control individuals. The relative MS risk, attributable to HLA-DRB1*15 was 3.05 (chi2 = 22.25, p < 0.0001). The phenotype frequency (PF) of none of the MCP-3 alleles was significantly altered in the population of controls versus unselected MS patients. When MS patients and control subjects were stratified according to positivity for HLA-DRB1*15, the MCP-3*A4-associated risk for developing MS decreased to 0.36 (p = 0.011). In the stratified groups of patients who were negative for both HLA-DRB1*15 and HLA-DRB1*03, and hence possessed a lower risk to develop MS, the MCP-3*A2-associated risk for MS development decreased significantly (p = 0.018). We conclude that the MCP-3*A4 allele might protect against MS development on the background of the increased risk in HLA-DRB1*15+ individuals and the MCP-3*A2 allele seems protective in low-risk individuals, who are both negative for DRB1*03 and DRB1*15.
Fiten
P
P
Rega Institute for Medical Research, Laboratory of Molecular Immunology, University of Leuven, Belgium.
Vandenbroeck
K
K
Dubois
B
B
Van Coillie
E
E
Nelissen
I
I
Van Damme
J
J
Ligers
A
A
Hillert
J
J
Andersson
M
M
Olsson
T
T
Opdenakker
G
G
D000483:Alleles; D054410:Chemokine CCL7; D016207:Cytokines; D015342:DNA Probes; D004276:DNA, Satellite / Q000032:analysis; D004742:Enhancer Elements, Genetic / Q000235:genetics / Q000276:immunology; D006684:HLA-DR Antigens / Q000032:analysis; D059811:HLA-DRB1 Chains; D006650:Histocompatibility Testing; D006801:Humans; D018945:Monocyte Chemoattractant Proteins / Q000235:genetics*; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology; D010641:Phenotype; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics* / Q000276:immunology
C515450:CCL7 protein, human; D054410:Chemokine CCL7; D016207:Cytokines; D015342:DNA Probes; D004276:DNA, Satellite; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D018945:Monocyte Chemoattractant Proteins