Haplotype analysis of the CD11 gene cluster in patients with chronic Helicobacter pylori infection and gastric ulcer disease.
Helicobacter pylori infection leads to a broad spectrum of disease manifestations such as gastritis, ulcer disease, and even gastric carcinoma. The genetically determined immune response and subsequent inflammation influence the degree of mucosal damage. Adhesion molecules of the CD11 cluster play an important role in adherence of neutrophils to endothelial cells in inflammation. We conducted a haplotype-based analysis of the CD11 cluster in a sample of 315 patients with H. pylori infection and investigated associations with gastric erosions and ulcer disease. Twelve single nucleotide polymorphisms (SNPs) covering the genes CD11a, CD11b, and CD11c were genotyped by Taqman technology. Linkage disequilibrium (LD) was assessed within the CD11 cluster and haplotype case-control analysis was conducted. Sliding window haplotype analysis identified a haplotype consisting of the markers CD11c exon 15 and intron 31 associated with gastric ulcer disease. Patients carrying the haplotype GA bear a 2.4-fold increased risk. No significant associations of single markers with disease outcome were found. High-density LD mapping and mutation detection of CD11c in larger samples will be necessary to confirm our findings and identify the causative variant. Thus, we conclude that genetic variants in the CD11 cluster may play a role in the development of gastric ulcer in chronic H. pylori infection presumably by influencing leukocyte adhesion. The biological effect of genetic variants of CD11c in gastric inflammation needs further clarification.