TLR1 and PRKAA1 Gene Polymorphisms in the Development of Atrophic Gastritis and Gastric Cancer

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.

PRKAA1 rs13361707 C/T polymorphism confers decreased susceptibility to esophageal cancer: A case‐control study

“…19 A study from Europe with mixed Caucasian populations obtained negative results for the association between this SNP and GC risk. 20 However, a recent meta-analysis combining all included studies showed no relationship between this SNP and GC risk in Asians. 21 breast cancer risk.…”

High Expression of Citron Kinase Contributes to the Development of Esophageal Squamous Cell Carcinoma

“…Among these genes, PRKAA1, SQSTM1, and IL6 are closely related to cell proliferation and apoptosis. PRKAA1 encodes for the adenosine monophosphate activated protein kinase (AMPK), which regulates tumor growth and proliferation by regulating energy metabolism ( Dargiene et al, 2018 ). He et al pointed out that LINC00473 regulated ESCC development through the miR-497-5p/PRKAA1 axis ( He, 2019 ).…”

Molecular Alterations in Gastric Intestinal Metaplasia

“…Various gene polymorphisms have been extensively studied as potential biomarkers for disease prediction, including premalignant gastric conditions and gastric cancer [ 33 , 34 , 35 , 36 , 37 , 38 ]. The most recent advancements in genomics enable scientists to identify single nucleotide polymorphisms (SNPs), which are the most frequent type of genetic variations in humans [ 39 , 40 ].…”