TLR1 and PRKAA1 Gene Polymorphisms in the Development of Atrophic Gastritis and Gastric Cancer
Gintare Dargiene1, Greta Streleckiene2, Jurgita Skieceviciene1, Marcis Leja3, Alexander Link4, Thomas Wex5, Limas Kupcinskas1, Peter Malfertheiner4, Juozas Kupcinskas1
1) Department of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania;
2) Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania;
3) Institute for Clinical and Preventive Medicine, University of Latvia, Riga, Latvia;
4) Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany;
5) Medical Laboratory for Clinical Chemistry, Microbiology and Infectious Diseases, Department of Molecular Genetics, Ottovon- Guericke University, Magdeburg, Germany
ABSTRACT Background & Aims: Previous genome-wide association studies showed that genetic polymorphisms in toll-like receptor 1 (TLR1) and protein kinase AMP-activated alpha 1 catalytic subunit (PRKAA1) genes were associated with gastric cancer (GC) or increased Helicobacter pylori (H. pylori) infection susceptibility. The aim of this study was to evaluate the association between TLR1 and PRKAA1 genes polymorphisms and H.
pylori infection, atrophic gastritis (AG) or GC in the European population. Methods: Single-nucleotide polymorphisms (SNPs) were analysed in 511 controls, 340 AG patients and 327 GC patients. TLR1 C>T (rs4833095) and PRKAA1 C>T (rs13361707) were genotyped by the real-time polymerase chain reaction. H. pylori status was determined by testing for anti-H. pylori IgG antibodies in the serum. Results: The study included 697 (59.2%) H. pylori positive and 481 (40.8%) H. pylori negative cases. We observed similar distribution of TLR1 and PRKAA1 alleles and genotypes in H. pylori positive and negative cases. TLR1 and PRKAA1 SNPs were not linked with the risk of AG. TC genotype of TLR1 gene was more prevalent in GC patients compared to the control group (29.7% and 22.3% respectively, p=0.002). Carriers of TC genotype had a higher risk of GC (aOR=1.89, 95% CI: 1.26–2.83, p=0.002). A similar association was observed in a dominant inheritance model for TLR1 gene SNP, where comparison of CC+TC vs. TT genotypes showed an increased risk of GC (aOR=1.86, 95% CI: 1.26–2.75, p=0.002). No association between genetic polymorphism in PRKAA1 gene and GC was observed. Conclusions: TLR1 rs4833095 SNP was associated with an increased risk of GC in a European population, while PRKAA1 rs13361707 genetic variant was not linked with GC. Both genetic polymorphisms were not associated with H. pylori infection susceptibility or the risk of AG. Key words: Helicobacter pylori − TRL1 − PRKAA1 − gastric cancer − atrophic gastritis. Abbreviations: AG: atrophic gastritis; AMPK: adenosine monophosphate-activated protein kinase; GC: gastric
cancer; H. pylori: Helicobacter pylori; PRKAA1: protein kinase AMP-activated alpha 1 catalytic subunit; SNPs:
single-nucleotide polymorphisms; TRL1: toll-like receptor 1.