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Re: Role of IL-10 promotor haplotypes in Helicobacter pylori associated gastric inflammation

We read with great interest the article by Rad and coworkers[1] 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 IL-10 promotor 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 and coworkers identified pathogenicity genes of H.pylori isolates by PCR based techniques from gastric biopsies. However, the human stomach is colonized not only by a single strain of H.pylori which obscures the investigation of germline mutations and host specific colonisation.[2] 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.[3] Thus, the identification of bacterial virulence factors is directly dependent on the localisation of the biopsy. That means, if cagA+,vacAs1+ and babA2 were not detected in biopsy specimen the cocolonisation with strains harbouring these genes at another localisation 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 to 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 the 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 were 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 found between any of the SNPs tested and H.pylori related pathologic findings (data not shown). The proinflammatory low secreting haplotype ATA did not confer a risk factor for the development of an ulcer as well as the contrainflammtory haplotype GCC did not protect the patients from gastric ulcer (Table I).

Table 1: Haplotype analysis of the IL-10 promotor in 427 patients with chronic gastritis and gastric ulcer disease (OR=odds ratio)

4. Hida N, Shimoyama T, Jr., Neville P et al. Increased expression of IL-10 and IL-12 (p40) mRNA in Helicobacter pylori infected gastric mucosa: relation to bacterial cag status and peptic ulceration. J Clin Pathol 1999;52: 658-64.