Is the monocyte chemotactic protein-1 -2518 G allele a risk factor for severe acute pancreatitis?
OBJECTIVE
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.
Papachristou
Georgios I
GI
Department of Medicine, University of Pittsburgh, Pennsylvania 15213, USA.
Sass
David A
DA
Avula
Haritha
H
Lamb
Janette
J
Lokshin
Anna
A
Barmada
M Michael
MM
Slivka
Adam
A
Whitcomb
David C
DC
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000097:blood / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010195:Pancreatitis / Q000097:blood / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011446:Prospective Studies; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D012720:Severity of Illness Index
D018932:Chemokine CCL2