Interleukin 1 Polymorphisms, Lifestyle Factors, and Helicobacter pylori Infection

Abstract

Associations between Key words: Helicobacter pylori infection -Interleukin 1 -Lifestyle factorsHelicobacter pylori (HP) infection, a well-known risk factor for stomach cancer, depends largely on sanitary conditions, especially in childhood. [1][2][3] There are still substantial differences in childhood prevalence between developed and developing countries, ranging from 4% to 82% reportedly.2) An increase in infected individuals with age is observed in many developed countries, which is considered to be due to a cohort effect. 1) Although there is no doubt that exposure to the bacterium increases the infection rate in the population, host susceptibility is also an important factor. Even after an ordinary level of HP exposure, uninfected persons still seem to exist in any population. In addition, spontaneous eradication after childhood infection may be influenced by host factors.Polymorphisms of interleukin-1β gene (IL-1B) and interleukin 1 receptor antagonist gene (IL-1RN) were reportedly associated with stomach cancer risk for a population from Poland. 4) IL-1β is a pro-inflammatory cytokine with multiple biological effects, 5) and is induced by HP infection.6) IL-1B has three diallelic polymorphisms at −511, −31, and 3954 base pairs (bp) from the transcriptional start site. Though the differences were not statistically significant, persistent HP infection was observed for 60% of individuals harboring the C/C genotype (n=58) at −31 of IL-1B, for 73% of those with the C/T genotype (n=67), and for 79% of those with the T/T genotype (n=24) in a population from Scotland.4) The T allele at −31 forms a TATA box, suspected of enhancing gene expression. The study reported that the polymorphism at −511 linked tightly with the polymorphism at −31, and therefore quite similar findings on the risks of stomach cancer and HP infection were obtained for IL-1B C−511T. The polymorphism at 3954 was not associated with the risks of stomach cancer and HP infection in the study.4) IL-1RN has a penta-allelic 86-bp tandem repeat polymorphism in intron 2, which was found to affect IL-1β production in vitro, 7) but it was not associated with HP infection. 4) IL-1α is another member of IL-1, which is encoded by IL-1A. It is primarily a cytosolic cytokine. About 10% or 15% is myristoylated and transported to the cell surface (membrane IL-1), but it is not detected in the serum under normal conditions. 5) IL-1A was reported to have three polymorphisms; C−889T, 46-bp variable number of tandem 6 To whom correspondence should be addressed.

Interleukin‐1B (IL‐1B) polymorphisms and gastric mucosal levels of IL‐1β cytokine in Korean patients with gastric cancer

“…However, the IL-1RN*2 homozygous allele was not found. Our results are similar with other East Asian studies on the IL-1 polymorphism, with the frequency of the IL-1RN*2 allele 1% in Japanese 24 and 2.5% in Taiwanese. 42 We could not find any association between the IL-1RN genotype and the risk of developing GC in this Korean population.…”

“…In the study on Japanese people, the corresponding values were 0.010, 0.438, 0.552 and 0.000 in H. pylori-infected patients without GC. 24 In the present study, the corresponding values were 0.005, 0.516, 0.478 and 0.001 in the control group and 0.004, 0.491, 0.499 and 0.004 in the GC group. Although the linkage disequilibrium coefficients in this study were similar to those of the study on Caucasian subjects, the haplotype pattern of IL-1B-511/IL-1B-31 related to the risk of GC was in the opposite direction.…”

“…Western 20 and Japanese reports 24 and this study found strong linkage disequilibrium between the IL-1B-31 and IL-1B-511 alleles. El-Omar et al 20 reported that the alleles at position 31 were tightly linked with those at position 511: 0.005 for the C-C combination, 0.375 for C-T, 0.610 for T-C and 0.010 for T-T among the controls in Scotland, and 0.000 for C-C, 0.298 for C-T, 0.699 for T-C and 0.002 for T-T among the controls in Poland.…”

“…For the polymorphism at position 889 in the promoter region of the IL-1A, the polymerase chain reaction with confronting two-pair primers (PCR-CTPP) was used (Table II); this does not require a step to digest PCR products for single nucleotide polymorphism genotyping. 24 This biallelic polymorphism produces a C allele of 428 and 279 base pairs (bp), and a T allele of 428 bp and 186 bp. A single bp polymorphism at position 31 in the promoter region of the IL-1B was analyzed by PCR of restriction fragment length polymorphisms (RFLPs).…”

“…32,33 The polymorphism at 3954 is not associated with the risk of GC and H. pylori infection. 24 The T allele at Ϫ31, but not Ϫ511, in the promoter region of the IL-1B forms a TATA box, suspected of enhancing gene expression and induction of IL-1␤. A breakthrough in the investigation of H. pylori-associated diseases was the discovery that polymorphisms of IL-1B-511T/IL-1B-31C and IL-1RN*2 alleles are significantly associated with the occurrence of hypochlorhydria and GC among Caucasians.…”