ORIGINAL ARTICLE

Influence of cytokine and ICAM-1 gene polymorphisms on susceptibility to chronic pancreatitis

W M Howell¹, P J Pead¹, F W Shek², M J Rose-Zerilli¹, T Armstrong³, C D Johnson³, D R Fine², J P Iredale² and A C Bateman⁴

¹ The Pancreatic and Liver Fibrosis Research Groups, Divisions of Human Genetics, Allergy and Repair, University of Southampton, Southampton SO16 6YD, UK
² The Pancreatic and Liver Fibrosis Research Groups, Divisions of Inflammation, Allergy and Repair, University of Southampton
³ The Pancreatic and Liver Fibrosis Research Groups, Department of Surgery, University of Southampton
⁴ Department of Cellular Pathology, Southampton University Hospitals NHS Trust, Southampton SO16 6YD, UK

Correspondence to:
Correspondence to:
Dr W M Howell
Department of Molecular Histocompatibility and Immunogenetics, National Blood Service, Holland Drive, Newcastle Upon Tyne, NE2 4NQ, UK; martin.howell{at}nbs.nhs.uk

Aims: 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 1ß (IL-1ß), IL-6, IL-8, tumour necrosis factor (TNF) and vascular endothelial growth factor (VEGF) gene promoter regions and the transforming growth factor ß1 (TGFß1) 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 ² 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-1ß, IL-6, or TNF proinflammatory cytokines genes or the TGFß1 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.

Abbreviations: ARMS, amplification refractory mutation system; HLA, human leucocyte antigen; ICAM-1, intercellular cell adhesion molecule 1; IL, interleukin; PCR, polymerase chain reaction; SNP, single nucleotide polymorphism; TGFß1, transforming growth factor ß1; TNF, tumour necrosis factor ; VEGF, vascular endothelial growth factor

Keywords: chronic pancreatitis; polymorphism; cytokine; intercellular adhesion molecule 1

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