Regular Article
A Novel Polymorphism in the MCP-1 Gene Regulatory Region That Influences MCP-1 Expression

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Abstract

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-1β-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-1β-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.

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