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) on the influence of cytokine gene polymorphisms on mucosal cytokine expression, gastric inflammation, and host specific colonisation in Helicobacter pylori infection. The authors reported an association of the contrainflammatory interleukin 10 (IL-10) promoter haplotype (GCC) with higher mucosal mRNA levels and colonisation with more virulent cagA+, vacAs1+, and babA2+ strains in 207 patients with H pylori induced chronic gastritis. Rad et al identified pathogenicity genes of H pylori isolates by polymerase chain reaction based techniques from gastric biopsies.
However, the human stomach is colonised by more than one strain of H pylori, which obscures the investigation of germline mutations and host specific colonisation.1 Moreover, within an apparently homogeneous population, remarkable genetic differences exist among single colony isolates. The capacity of H pylori to lose and possibly acquire exogenous DNA is consistent with a model of continuous microevolution within its cognate host.2 Thus identification of bacterial virulence factors is directly dependent on localisation of the biopsy. This means that if cagA+, vacAs1+, and babA2 were not detected in biopsy specimens, cocolonisation with strains harbouring these genes at another location cannot be excluded. Interestingly, the degree of inflammation and frequency of gastric atrophy and intestinal metaplasia was not different in patients carrying pro- or contrainflammatory haplotypes. The significance of genetic association studies is highly dependent on a well defined phenotype. In contrast with the degree of granulocytic and lymphocytic infiltration in chronic gastritis, which may again vary regionally, the development of gastric ulcer is an unambiguous hallmark for the severity of H pylori induced mucosal damage.
We recruited 614 consecutive Caucasian patients from Northern Germany who underwent gastroscopy with confirmed H pylori infection by rapid urease test or histology. Endoscopic findings and results of histopathological examination of biopsies, classified according to the Sydney classification, were recorded. In total, 316 patients presented with chronic gastritis and served as controls and 124 patients suffered from gastric ulcer. DNA was extracted by standard techniques from 5 ml of EDTA blood. All patients were genotyped for IL-10 −1082, −819, and −592 by TaqMan technology. Samples were recoded and genotypes assigned without knowledge of clinical status. Single marker and haplotype analysis was conducted to assess associations with development of gastric ulcer.
There were no associations between any of the single nucleotide polymorphisms tested and H pylori related pathological findings (data not shown). The proinflammatory low secreting haplotype ATA did not confer a risk factor for the development of an ulcer and the contrainflammatory haplotype GCC did not protect patients from gastric ulcer (table 1). Our results are in agreement with the study of Hida et al who reported higher IL-10 mRNA expression in cagA+ H pylori gastritis, with no relation to endoscopic diagnosis.3 Therefore, we conclude that genetic variations in the IL-10 promoter may influence mucosal cytokine expression but pro- and contrainflammatory haplotypes do not influence the clinical course of gastric inflammation, at least in Northern Germany. Furthermore, we suggest that association studies of germline polymorphisms with the outcome of chronic H pylori infection should focus on clearly defined phenotypes such as ulcer disease, gastric carcinoma, or primary gastric B cell lymphoma.
Conflict of interest: None declared.
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