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Is the monocyte chemotactic protein-1 -2518 G allele a risk factor for severe acute pancreatitis?
Georgios I Papachristou1, David A Sass, Haritha Avula
1Department of Medicine, University of Pittsburgh, Pennsylvania 15213, USA.
Background & Aims:
Acute pancreatitis (AP) reflects the intensity of the inflammatory response and is divided into mild AP (MAP) or severe AP (SAP). Monocyte chemotactic protein-1 (MCP-1) gene expression is altered by an A/G polymorphism (-2518), with the G allele increasing MCP-1 production. Our aim was to determine whether the MCP-1 -2518 A/G polymorphism affects the severity of AP.
Methods:
Seventy-seven consecutive patients and 116 controls were evaluated. The A/G genotype was evaluated by polymerase chain reaction amplification, restriction fragment length polymorphism, and DNA sequencing. MCP-1 serum levels were quantified using a fluorescence bead-based immunoassay.
Results:
Sixty-three of 77 patients had MAP (82%) and 14 of 77 had SAP (18%). Patients with SAP had a significantly greater proportion of the G allele (12 of 14; 86%) than did control subjects (50 of 116; 43%) (odds ratio [OR], 7.9; 95% confidence interval [CI], 1.7-37, P < .003) or MAP patients (29 of 63; 46%) (OR, 7.0; 95% CI, 1.5-34; P < .007). Patients with pancreatitis and AA genotype had a low risk for SAP (OR, .13; 95% CI, .01-.61; P < .003). As predicted by the genotype, the serum MCP-1 levels were significantly higher in the SAP patients when compared with the MAP patients ( P = .002) and they also predicted death.
Conclusions:
MCP-1 -2518 G allele is a risk factor for severe AP. MCP-1 serum levels, measured early in the course of AP, appear to be an accurate predictor of severity of acute pancreatitis and death.
Insights
The G allele of the Monocyte Chemotactic Protein-1 (MCP-1) gene polymorphism is a risk factor for severe acute pancreatitis (AP). Higher MCP-1 serum levels in AP patients predict disease severity and mortality.
Area of Science:
- Genetics and immunology research.
- Investigating molecular mechanisms of inflammatory diseases.
Background:
- Acute pancreatitis (AP) severity ranges from mild (MAP) to severe (SAP).
- Monocyte Chemotactic Protein-1 (MCP-1) production is influenced by a -2518 A/G gene polymorphism, with the G allele linked to increased MCP-1.
- Understanding genetic predispositions to AP severity is crucial.
Purpose of the Study:
- To investigate if the MCP-1 -2518 A/G polymorphism influences the severity of acute pancreatitis.
- To determine the association between MCP-1 genotype and AP classification (MAP vs. SAP).
Main Methods:
- Genotyping of the MCP-1 -2518 A/G polymorphism using PCR, RFLP, and DNA sequencing in 77 AP patients and 116 controls.
- Quantification of serum MCP-1 levels via fluorescence bead-based immunoassay.
- Statistical analysis to compare allele frequencies and serum levels between patient groups.
Main Results:
- The G allele was significantly more prevalent in severe AP (SAP) patients (86%) compared to controls (43%) and mild AP (MAP) patients (46%).
- Patients with the AA genotype had a reduced risk of developing SAP.
- Serum MCP-1 levels were significantly higher in SAP patients than in MAP patients and correlated with mortality.
Conclusions:
- The MCP-1 -2518 G allele is identified as a genetic risk factor for severe acute pancreatitis.
- Early measurement of serum MCP-1 levels can accurately predict AP severity and patient outcomes, including death.
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