Polymorphisms of TLR9 gene are associated with a decreased risk of H. pylori infection in a Chinese population

Abstract

Background: A series of evidence suggests that genetic variation in toll-like receptor (TLR) 9 might influence the outcome of Helicobacter pylori (H. pylori) infection and play an important role in gastric carcinogenesis.Methods: We conducted a case-control study to evaluate TLR9 polymorphisms on the risk of H. pylori infection and non-cardia gastric cancer (GC) in a Chinese population. We genotyped a tagging singlenucleotide polymorphism (SNP), rs164640, and a potentially functional SNP, rs187084, by TaqMan technique among 288 patients with non-cardia GC and 281 controls. Unconditional logistic regression (LR) was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for SNPs in association with H. pylori infection and non-cardia GC risk.Results: Our results indicated that among normal controls, the minor allele homozygotes of both SNPs were significantly associated with a decreased risk of H. pylori infection when compared with their major allele homozygotes (for rs164640: OR =0.41, 95% CI, 0.18-0.93; for 187084: OR =0.38, 95% CI, 0.17-0.85).However, neither of the two SNPs demonstrated a significant association with non-cardia GC risk.Conclusions: Our results revealed that TLR9 polymorphisms might have effects on the risk of H. pylori infection, but they do not seem to contribute to the risk of non-cardia GC in our studied population.

Common variants in toll-like receptor family genes and risk of gastric cancer: a systematic review and meta-analysis

“…For these studies, only the SNPs that followed the HWE were included in the meta-analysis. Finally, a total of 45 publications ( Zeng et al, 2011a ; de Oliveira and Silva, 2012 ; Castano-Rodriguez et al, 2014 ; Castaño-Rodríguez et al, 2014 ; Companioni et al, 2014 ; Dargiene et al, 2018 ; Eed et al, 2020 ; Gao et al, 2020 ; Li et al, 2021 ; Sultan et al, 2022 ; Garza-Gonzalez et al, 2007 ; Hold et al, 2007 ; Tahara et al, 2007 ; Santini et al, 2008 ; Trejo-de la et al, 2008 ; Hishida et al, 2009 ; Hold et al, 2009 ; Hishida et al, 2010 ; Huang et al, 2010 ; Rigoli et al, 2010 ; Zeng et al, 2011b ; Kupcinskas et al, 2011 ; Schmidt et al, 2011 ; De Oliveira et al, 2013 ; He et al, 2013 ; Kim et al, 2013 ; Wang et al, 2013 ; Huang et al, 2014 ; Kutikhin et al, 2014 ; Li et al, 2014 ; Qadri et al, 2014 ; He et al, 2015 ; Liu et al, 2015 ; Ravishankar Ram et al, 2015 ; Stubljar et al, 2015 ; Wei et al, 2015 ; Mukherjee et al, 2016 ; Simawaranon et al, 2017 ; Xu et al, 2017 ; He et al, 2018a ; De Re et al, 2019 ; Huang et al, 2019 ; Susi et al, 2019 ; Tongtawee et al, 2019 ; de Matos Lourenço et al, 2020 ; Gonzalez-Hormazabal et al, 2021 ), with a total sample size of 25,831 participants (cases: 11,308; controls: 14,523), examining the relation of 18 different SNPs in the TLR family to GC, were eligible to be included in the present meta-analysis. The analyzed studies were published from 2007 to 2022.…”

“…The analyzed studies were published from 2007 to 2022. Moreover, we systematically reviewed the results of the studies on less common SNPs of TLRs and GC that were not eligible for meta-analysis (with only one available effect size) ( Zeng et al, 2011b ; Kim et al, 2013 ; Yang et al, 2013 ; Castano-Rodriguez et al, 2014 ; Companioni et al, 2014 ; Liu et al, 2015 ; De Re et al, 2019 ; Wang et al, 2019 ; Gao et al, 2020 ; Gonzalez-Hormazabal et al, 2021 ; Li et al, 2021 ) to have a comprehensive evaluation. Of the included studies in the meta-analysis, 12 studies were on Caucasian populations ( Hold et al, 2007 ; Santini et al, 2008 ; Hold et al, 2009 ; Rigoli et al, 2010 ; Kupcinskas et al, 2011 ; Companioni et al, 2014 ; Kutikhin et al, 2014 ; Stubljar et al, 2015 ; Dargiene et al, 2018 ; De Re et al, 2019 ; Eed et al, 2020 ; Sultan et al, 2022 ), seven studies were on Latino populations ( Garza-Gonzalez et al, 2007 ; Trejo-de la et al, 2008 ; de Oliveira and Silva, 2012 ; De Oliveira et al, 2013 ; Susi et al, 2019 ; de Matos Lourenço et al, 2020 ; Gonzalez-Hormazabal et al, 2021 ), and 26 studies were on Asian populations.…”

“…In the study by Gonzalez-Hormazabal et al (2021) in Chile on TLR-4-2 rs7656411, TLR-4 rs1554973, TLR-4 rs7037117, TLR-4 rs913930, and TLR-5 rs75977922, a significantly increased odds of GC was observed for carriers of the variant allele/genotype of TLR-5 rs75977922. No significant association was identified between the TLR-1 rs5743681 in German ( Yang et al, 2013 ), TLR-2 rs1898830 in Korean ( Kim et al, 2013 ), TLR-8 rs3764880 in Italian ( De Re et al, 2019 ), and TLR-9 rs164640 in Chinese ( Gao et al, 2020 ) populations and the risk of GC. In contrast, variations in TLR-3 1377C T (rs3775290) ( Liu et al, 2015 ) and TLR-4 rs1057317 ( Trejo-de la et al, 2015 ; Wang et al, 2019 ) in Chinese populations were significantly linked to the increased risk of GC among the risk-allele carriers.…”

“…Gastric cancer (GC) is the fifth most prevalent kind of malignancy and the third main cause of cancer-related death globally ( Castano-Rodriguez et al, 2014 ), accounting for 8.8% of total cancer-associated mortalities, with 5-year survival rates less than 30% ( Castaño-Rodríguez et al, 2014 ). GC is a complex disease with a multifactorial etiology that includes the combined impacts of lifestyle, bacteria, and host and environmental factors ( Gao et al, 2020 ). However, Helicobacter pylori infection is an established risk factor for GC, but only 0.1%–4% of infected people develop GC, highlighting the etiological involvement of environmental predisposing factors and host genetics in GC development ( Companioni et al, 2014 ).…”

“…Furthermore, TLR-7 expression has been negatively linked to the viability of GC cells ( Jiang et al, 2016 ), and the TLR-7 agonist has been examined as a possible vaccine formulation in GC immunotherapy ( Wang X-D. et al, 2015 ). TLR-9 is also expressed aberrantly in GC, and H. pylori DNA could trigger TLR-9-mediated GC cell invasion ( Gao et al, 2020 ). Single-nucleotide polymorphisms (SNPs) within TLR genes may lead to a change in their expression along with dysregulation of their signaling pathways, resulting in disturbed secretion of inflammatory mediators and enabling H. pylori to cause persistent infection and affecting gastric immunopathology and GC susceptibility ( Eed et al, 2020 ; Sultan et al, 2022 ).…”