Influence of cytokine and ICAM-1 gene polymorphisms on susceptibility to chronic pancreatitis.
OBJECTIVE
To test the hypothesis that single nucleotide polymorphisms (SNPs) within genes (or their promoter regions) encoding cytokines, growth factors, and intercellular adhesion molecules modulate the risk of development of chronic pancreatitis (CP).


METHODS
DNA was extracted from peripheral blood leucocytes or formalin fixed, paraffin wax embedded tissue from 53 patients with CP and 266 healthy controls. SNPs within the interleukin 1beta (IL-1beta), IL-6, IL-8, tumour necrosis factor alpha (TNFalpha) and vascular endothelial growth factor (VEGF) gene promoter regions and the transforming growth factor beta1 (TGFbeta1) and intercellular cell adhesion molecule 1 (ICAM-1) genes were genotyped by the amplification refractory mutation system polymerase chain reaction or 5' nuclease (Taqman) techniques. Patient-control comparisons were made using 2 x 2 contingency tables and chi2 analyses.


RESULTS
A non-significant decrease in the frequency of the IL-8 -251 AA genotype and a non-significant increase in the frequency of the ICAM-1 +469 GA genotype was seen in patients compared with controls. No associations were identified between SNPs in the promoter regions of the IL-1beta, IL-6, or TNFalpha proinflammatory cytokines genes or the TGFbeta1 and VEGF genes and susceptibility to CP.


CONCLUSIONS
This preliminary study suggests that genetic polymorphism within several cytokine genes is unlikely to influence susceptibility to CP, but the possible role of IL-8 and ICAM-1 polymorphisms in the development of this disease requires further investigation.
Howell
W M
WM
The Pancreatic and Liver Fibrosis Research Groups, Divisions of Human Genetics, Allergy and Repair, University of Southampton, Southampton SO16 6YD, UK. martin.howell@nbs.nhs.uk
Pead
P J
PJ
Shek
F W
FW
Rose-Zerilli
M J
MJ
Armstrong
T
T
Johnson
C D
CD
Fine
D R
DR
Iredale
J P
JP
Bateman
A C
AC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010195:Pancreatitis / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide
D016207:Cytokines; D018799:Intercellular Adhesion Molecule-1