Helicobacter pylori vacA d1/-i1 Genotypes and Geographic Differentiation between High and Low Incidence Areas of Gastric Cancer in Iran

Helicobacter pylori (H. pylori)-specific genotypes have been closely correlated with an increased risk of gastric cancer (GC). The present study aimed to determine the distribution of H. pylori pathogenic genotypes amongst Iranians infected with strains representing European ancestry in areas with different GC incidence. A total of 138 H. pylori isolates from ten districts in Iran were used for genotyping. The following genotypic frequency was observed: vacA s1 (94.9%), s2 (5.1%), m1 (24.6%), m2 (75.4%), d1 (39.9%), d2 (60.1%), i1 (40.6%), i2 (59.4%), iceA1 (76.8%), iceA2 (52.9%), iceA1/2 (29.7%), babA2 (40.6%), and cagA (65.9%). Hierarchical analyses of molecular variance (AMOVA) for the vacA d1, d2, i1, and i2 alleles and iceA1 and iceA1/2 genes found significant levels of genetic differentiation among populations (P < 0.05). Prevalence of the vacA d1, i1, and iceA1/2 (but not iceA1) genes and vacA d1/i1, vacA d1/iceA1, vacA d1/iceA1/2, vacA d1/cagA+, vacA i1/iceA1, vacA i1/iceA1/2, and vacA i1/cagA+ genotypes were significantly higher (>2- or 3-fold) among H. pylori isolates from high incidence GC areas that had age-standardized rates (ASRs) of >20/105 (max. 51.8/105) when compared with those from low incidence (ASRs <10/105) GC areas (P < 0.005, for the latter, P = 0.016). In contrast, the vacA d2/i2, m2/d2, and m2/i2 genotypes were significantly more prevalent in low compared to high incidence GC areas (P < 0.005). The results of Mantel''s test only showed a low correlation between genetic and geographic distances for the iceA1 and iceA1/2 (but not vacA alleles, iceA2, babA2, and cagA) genes among ten districts of Iran (r = 0.098 and 0.074, respectively, P < 0.05). We propose that the H. pylori vacA d1/-i1 genotypes, which are new determinants of GC, have tremendous potential for differentiating H. pylori strains from high and low incidence GC areas in Iran.