| Background:Helicobacter pylori have proven to be associated with gastritis, peptic ulcers, gastric cancer, and mucosa-associated lymphoid tissue lymphoma. H. pylori infection is related to the levels of economic, culture and medical care. In addition, host genetic polymorphisms are also associated with H. pylori susceptibility.Wuwei city was once the intersection of eastern and western civilizations and was an important city in the ancient Silk Road. Wuwei has a high occurrence of gastric cancer, and people in this area have a high prevalence of H. pylori. High prevalence of H. pylori may lead to high occurrence of gastric cancer. Based on meta-analysis of the relationship between IL-1B, TNF-A and IL-8 polymorphisms and H. pylori infection, we conducted this study focuses on the correlation between IL-1B, TNF-A and IL-8 gene polymorphisms and H. pylori susceptibility among a Chinese Han population of Wuwei in order to explore possible related mechanisms between the host’s genetic background and H. pylori infection in this area, which may provide evidence and develop new strategies for the prevention and cure of gastric cancer in this area.Materials and Methods:(1) Meta-analysis: Pubmed, Embase, Cochrane Library, CBM and CNKI were searched up to January 2016. Inclusion and exclusion criteria were created for screening studies. Data were analyzed with the Stata13.1 software package using pooled odds ratios(ORs) with 95% confidence intervals(CI).Sensitivity Analysis was performed by omitting each study in turn. Stratified analysis was conducted on H. pylori detection methods, study designs and ethnicities. Begg’s rank correlation test and Egger’s regression test were used to test publication bias. Hardy-Weinberg equilibrium was assessed by the χ2 test for goodness of fit, with a P-value less than 0.05 considered a significant deviation.(2) Association study: Genomic DNA of 662 recruited healthy participants of Han population who lived in Wuwei City was extracted from 5 ml of peripheral blood by the Genomic DNA kit. Cytokine gene variants was genotyped on the Sequenom Mass ARRAY platform, and H. pylori infection of the participants was detected by 14C-urea breath test. The correlation between the cytokine gene variants and H. pylori infection was examined by a χ2 test with ORs and 95%CI.Results:(1) Meta-analysis: IL-1B-31C>T polymorphism was positive correlated with H. pylori infection(TT+CT vs. CC, OR = 1.04, 95% CI = 0.91–1.18; TT vs. CT+CC, OR = 1.10, 95% CI = 1.00–1.20; TT vs. CC, OR = 1.16, 95% CI = 1.04–1.30; T allele vs. C allele, OR = 1.04, 95% CI = 0.96–1.13), and was positive correlated with H. pylori infection in the ELISA method subgroup, Asian subgroup and Population-based(PB) subgroup. IL-1B-511C>T also had significant association with H. pylori infection(TT+CT vs. CC, OR = 1.10, 95% CI = 0.98–1.23; TT vs. CT+CC, OR = 1.06, 95% CI = 0.97–1.16; TT vs. CC, OR = 1.10, 95% CI = 0.99–1.22; T allele vs. C allele, OR = 1.06, 95% CI = 1.00–1.11), and was positive correlated with H. pylori infection in Hospital-based(HB) subgroup.The TNF-A-308G>A polymorphism was associated with decreasing H. pylori infection in recessive and homozygote models(AA+AG vs. GG, OR = 0.91, 95% CI = 0.81–1.03; AA vs. AG+GG, OR = 0.67, 95% CI = 0.45–1.00; AA vs. GG, OR = 0.67, 95% CI = 0.45–0.99; A allele vs. G allele, OR = 0.90, 95% CI = 0.81–1.01). For the-1031T>C polymorphism, a significantly decreased risk was also found in recessive and homozygote models(CC+CT vs. TT, OR = 0.98, 95% CI = 0.82–1.17; CC vs. CT+TT, OR = 0.62, 95% CI = 0.46–0.84; CC vs. TT, OR = 0.62, 95% CI = 0.46–0.85; C allele vs. T allele, OR = 0.93, 95% CI = 0.80–1.09).-863C>A polymorphism and-857C>T polymorphism had no significant association with H. pylori infection. A subgroup analysis was conducted on H. pylori detection methods, and the results showed that-857C>T polymorphism and-1031T>C polymorphism significantly decreased the risk of H. pylori infection in the non-ELISA subgroup. We also conducted a subgroup analysis on ethnicity. The results showed that the-1031T>C polymorphism was associated with H. pylori infection for the Asian subgroup. A stratified analysis on study design was also performed, and the results indicated that-863C>A significantly increased the risk and-1031T>C decreased the risk for HB subgroups.The IL-8-251T>A polymorphism had a significant association with H. pylori infection in the homozygous and allelic models(AA+TA vs. TT, OR = 1.12, 95% CI = 0.94-1.33; AA vs. TA+TT, OR = 1.06, 95% CI = 0.92-1.22; AA vs. TT, OR = 1.17, 95% CI = 1.00-1.37; A allele vs. T allele, OR = 1.07, 95% CI = 1.00-1.16). The IL-8-251T>A polymorphism also significantly increased the risk of H. pylori infection in Asian subgroup, Non-ELISA subgroup and PB subgroup.(2) Association study: IL-1B-31C>T, IL-1B-511C>T, IL-1B-1473G>C, TNF-A-308G>A, TNF-A-863C>A, TNF-A-1031T>C and IL-8-251T>A polymorphisms of the 662 recruited healthy participants had no significant association with H. pylori susceptibility in Wuwei area(P>0.05).Conclusion:(1) The genotype TT of IL-1B-31C>T may increase the risk of H. pylori infection in Asian and Latin American population; the allele T of IL-1B-511C>T may increase the risk of H. pylori infection in multiethnic population.(2) The genotype AA of TNF-A-308G>A and genotype CC of TNF-A-1031T>C may decrease the risk of H. pylori infection in multiethnic population; TNF-A-857C>T and TNF-A-863C>A have no association with H. pylori infection.(3) The allele A of IL-8-251T>A may be a predisposing allele of H. pylori infection in multiethnic population.(4) IL-1B-31C>T, IL-1B-511C>T, IL-1B-1473G>C, TNF-A-308G>A, TNF-A-863C>A, TNF-A-1031T>C and IL-8-251T>A polymorphisms had no association with H. pylori susceptibility in Wuwei population.Further studies with larger samples and various ethnicities should be conducted to validate these results. |
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