A novel polymorphism in the MCP-1 gene regulatory region that influences MCP-1 expression.
Two novel polymorphisms in the distal regulatory region of the MCP-1 gene were identified by directly sequencing PCR amplified genomic DNA. These polymorphisms are located at positions -2518 (G or A) and -2076 (A or T) relative to the major transcriptional start site of the gene. To examine the effect of these polymorphisms on MCP-1 transcription, polymorphic variants of the MCP-1 distal regulatory region were placed upstream of a luciferase reporter gene and transfected into A172 cells. IL-1beta-induced luciferase activity was significantly greater from cells transfected with constructs containing G at position -2518. The polymorphism at -2076 did not affect MCP-1 transcription. IL-1beta-treated peripheral blood mononuclear cells from individuals heterozygous or homozygous for G at -2518 produced more MCP-1 than cells from individuals homozygous for A at -2518. These data identify a polymorphism in the MCP-1 distal regulatory region that affects the level of MCP-1 expression in response to an inflammatory stimulus.
Rovin
B H
BH
Department of Medicine, Ohio State University School of Medicine and Public Health, Columbus, Ohio 43210, USA. rovin.1@osu.edu
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L
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Saxena
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D000483:Alleles; D018932:Chemokine CCL2 / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics; D017930:Genes, Reporter; D005838:Genotype; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007962:Leukocytes / Q000378:metabolism; D011110:Polymorphism, Genetic; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014162:Transfection; D014407:Tumor Cells, Cultured
D018932:Chemokine CCL2; D007375:Interleukin-1