| Summary: | The aim of this study was to define the relationship between several environmental, laboratory, and genetic factors, i.e., TLR2 and NLRP3 polymorphisms, and <i>Helicobacter pylori</i> (<i>H. pylori</i>) infection in children, by comparing three different groups of pediatric subjects: <i>H. pylori</i>-induced gastritis, non-<i>H. pylori</i> gastritis, and healthy controls. Our final study sample included 269 children, which were divided into three groups according to the histopathological exam: group 1 with 51 children with <i>H. pylori</i>-induced gastritis, group 2 with 103 children with <i>H. pylori</i>-negative gastritis, and group 3 (control group) with 115 children without any histopathological changes. All children underwent a thorough anamnesis, clinical exam, laboratory tests, and upper digestive endoscopy with gastric biopsy for rapid urease test, histopathological exam, and genetic analysis of <i>TLR2</i> rs3804099, <i>TLR2</i> rs3804100, and <i>NLRP3</i> rs10754558 gene polymorphisms. We noticed a significant association between living conditions and the type of gastritis (<i>p</i> < 0.0001). Both rapid urease and serological tests were significantly associated with the presence of <i>H. pylori</i> (<i>p</i> < 0.0001). The CT variant genotype of <i>TLR2</i> rs380499 was significantly associated with neutrophil count (<i>p</i> = 0.0325). We noticed a significant association between the CC variant genotype of <i>NLRP3</i> rs10754558 and leucocytes, neutrophils, eosinophils, as well as ALT (<i>p</i> = 0.0185, <i>p</i> = 0.0379, <i>p</i> = 0.0483, <i>p</i> = 0.0356). Based on these findings, we state that poor living conditions and rural areas represent risk factors for <i>H. pylori</i> infection. The rapid urease test is a reliable diagnostic tool for this infection. CT and TT carriers of <i>TLR2</i> rs3804099, as well as CC carriers of <i>NLRP3</i> rs10754558, might display a more severe degree of systemic inflammation.
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