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 mononuc lear cells, including monocytes and lymphocytes, the inflammatory cell type s that predominate in multiple sclerosis lesions. We studied the possible a ssociation between the presence of a CA/GA microsatellite repeat polymorphi sm in the promoter/enhancer region of the MCP-3 gene and the occurrence of multiple sclerosis. DNA samples from 192 Swedish multiple sclerosis (MS) pa tients and 129 healthy controls were analysed by an automated fluorescent t echnique. 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 significa ntly between MS patients and control individuals. The relative MS risk, att ributable to HLA-DRB1*15 was 3.05 (chi(2) = 22.25, p < 0.0001). The phenoty pe 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*3, and hence possessed a lower risk to develop MS, th e 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 devel opment on the background of the increased risk in HLA-DRB1*15(+) individual s and the MCP-3*A2 allele seems protective in low-risk individuals, who are both negative for DRB1*03 and DRB1*15. (C) 1999 Elsevier Science B.V. All rights reserved.