OBJECTIVES: The -A2518G variation in monocyte chemoattractant protein (MCP)-1 gene promoter has been associated with autoimmune diseases. Our aim was to investigate the gene polymorphism and MCP-1 plasma levels in patients with inflammatory bowel disease (IBD). METHODS: Family-based and case-control association analyses of the -A2518G polymorphism (rs1024611) were performed in 1,936 subjects (770 patients with Crohn's disease (CD), 316 patients with ulcerative colitis (UC), 302 healthy relatives (151 CD trios), and 548 healthy controls (HCs)). Extensive gene sequencing was also undertaken, and a further six single-nucleotide polymorphisms (SNPs) were genotyped in 435 CD patients and 189 HCs. MCP-1 protein plasma levels in 234 CD patients, 117 UC patients, and 108 HCs were assessed by an immunosorbent assay. RESULTS: Five SNPs in strong linkage disequilibrium (D'>0.85) were associated with CD, with the strongest signal found at the -A2518G SNP. The frequency of the G allele was significantly lower in CD patients (22.1%), compared with HCs (29.8%), both at case-control (P=6 x 10(-6)) and at transmission disequilibrium test analyses (T/U 41/88; P=4 x 10(-4)). No difference in alleles (26.1%) and genotype frequencies were found in UC patients. MCP-1 plasma levels in CD and UC patients were similar to those in HCs (P=0.38), irrespective of disease activity, or MCP-1 genotypes. However, 30 CD (13%) and 20 UC patients (17%) with extensive colonic involvement had plasma levels significantly higher than HCs (P=0.02). CONCLUSIONS: The -A2518G polymorphism seems to be associated with CD but does not influence MCP-1 plasma levels, which in contrast are increased in UC and CD with extensive colonic involvement.
OBJECTIVES: The -A2518G variation in monocyte chemoattractant protein (MCP)-1 gene promoter has been associated with autoimmune diseases. Our aim was to investigate the gene polymorphism and MCP-1 plasma levels in patients with inflammatory bowel disease (IBD). METHODS: Family-based and case-control association analyses of the -A2518G polymorphism (rs1024611) were performed in 1,936 subjects (770 patients with Crohn's disease (CD), 316 patients with ulcerative colitis (UC), 302 healthy relatives (151 CD trios), and 548 healthy controls (HCs)). Extensive gene sequencing was also undertaken, and a further six single-nucleotide polymorphisms (SNPs) were genotyped in 435 CD patients and 189 HCs. MCP-1 protein plasma levels in 234 CD patients, 117 UC patients, and 108 HCs were assessed by an immunosorbent assay. RESULTS: Five SNPs in strong linkage disequilibrium (D'>0.85) were associated with CD, with the strongest signal found at the -A2518G SNP. The frequency of the G allele was significantly lower in CD patients (22.1%), compared with HCs (29.8%), both at case-control (P=6 x 10(-6)) and at transmission disequilibrium test analyses (T/U 41/88; P=4 x 10(-4)). No difference in alleles (26.1%) and genotype frequencies were found in UC patients. MCP-1 plasma levels in CD and UC patients were similar to those in HCs (P=0.38), irrespective of disease activity, or MCP-1 genotypes. However, 30 CD (13%) and 20 UC patients (17%) with extensive colonic involvement had plasma levels significantly higher than HCs (P=0.02). CONCLUSIONS: The -A2518G polymorphism seems to be associated with CD but does not influence MCP-1 plasma levels, which in contrast are increased in UC and CD with extensive colonic involvement.
Authors: George P Christophi; Rong Rong; Philip G Holtzapple; Paul T Massa; Steve K Landas Journal: Inflamm Bowel Dis Date: 2012-03-29 Impact factor: 5.325
Authors: Minh-Hieu T Pham; Gregory B Bonello; John Castiblanco; Tuan Le; Jose Sigala; Weijing He; Srinivas Mummidi Journal: PLoS One Date: 2012-11-16 Impact factor: 3.240
Authors: Ruili Guan; Sharad Purohit; Hongjie Wang; Bruce Bode; John Chip Reed; R Dennis Steed; Stephen W Anderson; Leigh Steed; Diane Hopkins; Chun Xia; Jin-Xiong She Journal: PLoS One Date: 2011-04-12 Impact factor: 3.240
Authors: Melanie Craven; Charlotte E Egan; Scot E Dowd; Sean P McDonough; Belgin Dogan; Eric Y Denkers; Dwight Bowman; Ellen J Scherl; Kenneth W Simpson Journal: PLoS One Date: 2012-07-25 Impact factor: 3.240