Polymorphism and Evolutionary Analysis of Helicobacter pylori Ferric Uptake Regulator Gene Associated with Gastric Cancer
Objective:To explore the single nucleotide polymorphism(SNP)and evolutionary characteristics of the ferric uptake regulator(Fur)gene of Helicobacter pylori(Hp)associated with gastric cancer.Methods:150 Hp strains(59 strains from patients with gastric cancer and 91 strains from gastritis patients)were selected which were stored in Qingdao Municipal Hospital from 2011-2018.The fur gene was amplified by polymerase chain reaction(PCR),then the generation sequencing and SNP analysis were proceeded.226 Hp fur sequences of East Asia subgroup were downloaded from the NCBI database.SNPs were analyzed and a Neighbour-Joining phylogenetic tree was constructed to establish evolutionary typing using MEGA 5.0 software.Results:98.7%(148/150)of the Hp strains were positive for fur gene using PCR amplification.A synonymous SNP of base A→G(SNP A351G)existed at site 351 of the fur gene.The variation frequency of G allele had a significantly higher in gastric cancer strains than that of gastritis strains(x2=5.161,P=0.023).The risk of gastric cancer significantly increased in strains carrying this allele(OR=2.4).Neighbour-Joining phylogenetic tree was separated into two phylogenetic subgroups,type Ⅰ and type Ⅱ based on the sequence of the Hp East Asia fur gene.The prevalence of Hp strains of patients with gastric cancer was predominantly higher in the evolutionary type Ⅰ subgroup(x2=41.8,P=9.9×10-11).The risk of gastric cancer was significantly higher with fur gene evolutionary type Ⅰ(OR=4.7).Conclusion:Hp carrying fur SNP A351G caused a significantly higher risk of gastric cancer,and fur gene evolutionary type Ⅰ had an association with the risk of gastric carcinogenesis.
Helicobacter pyloriFerric uptake regulatorSingle nucleotide polymorphismEvolutionGastric cancer