Helicobacter pylori vac A genotype is a predominant determinant of immune response to Helicobacter pylori CagA

AIM To evaluate the frequency of Helicobacter pylori(H. pylori) Cag A antibodies in H. pylori infected subjects and to identify potential histopathological and bacterial factors related to H. pylori Cag A-immune response.METHODS Systematic data to H. pylori isolates, blood samples, gastric biopsies for histological and molecular analyses were available from 99 prospectively recruited subjects. Serological profile(anti-H. pylori, anti-Cag A) was correlated with H. pylori isolates(cag A, EPIYA, vac A s/m genotype), histology(Sydney classification) and mucosal interleukin-8(IL-8) m RNA and protein expression. Selected H. pylori strains were assessed for H. pylori Cag A protein expression and IL-8 induction in co-cultivation model with AGS cells.RESULTS Thirty point three percent of microbiologically confirmed H. pylori infected patients were seropositive for Cag A. Majority of H. pylori isolates were cag A gene positive(93.9%) with following vac A polymorphisms: 42.4% vac A s1m1, 23.2% s1m2 and 34.3% s2m2. Anti-Cag AIg G seropositivity was strongly associated with atrophic gastritis, increased mucosal inflammation according to the Sydney score, IL-8 and cag A m RNA expression. V a c A s a n d m p o l y m o r p h i s m s w e r e t h e m a j o r determinants for positive(vac A s1m1) or negative(vac A s2m2) anti-Cag A serological immune response, which also correlated with the in vitro inflammatory potential in AGS cells. In vitro co-cultivation of representative H. pylori strains with AGS cells confirmed functional Cag A translocation, which showed only partial correlation with Cag A seropositivity in patients, supporting vac A as major co-determinant of the immune response.CONCLUSION Serological immune response to H. pylori cag A + strain in H. pylori infected patients is strongly associated with vac A polymorphism, suggesting the crucial role of bacterial factors in immune and clinical phenotype of the infection.

Polymorphisms of micro RNA target genes IL12B, INSR, CCND1 and IL10 in gastric cancer

AIM To evaluate associations between mi RNA target genes IL12B,INSR,CCND1 and IL10 polymorphisms and gastric cancer(GC)in European population.METHODS Gene polymorphisms were analyzed in 508 controls and474 GC patients from 3 tertiary centers in Germany,Lithuania and Latvia.Controls were patients from the out-patient departments,who were referred for upper endoscopy because of dyspeptic symptoms and had no history of previous malignancy.Gastric cancer(GC)patients had histopathological verification of gastric adenocarcinoma.Genomic DNA was extracted using salting out method from peripheral blood mononuclear cells.IL12B T>G(rs1368439),INSR T>C(rs1051690),CCND1 A>C(rs7177)and IL10 T>C(rs3024498)SNPs were genotyped by the real-time polymerase chain reaction.Associations between gene polymorphism and GC were evaluated using multiple logistic regression analysis with adjustment for sex,age and country of birth.RESULTS We observed similar distribution of genotypes and allelic frequencies of all polymorphisms between GC patients and controls except of INSR rs1051690.The frequency of the T allele of INSR gene was significantly higher in GC patients than in controls(23.26%and 19.19%respectively,P=0.028).CT genotype was also more prevalent in patients compared to control group(38.48%and 30.12%respectively,P<0.021).Logistic regression analysis revealed that only one polymorphism(rs1051690 in INSR gene)was associated with increased risk of GC.Carriers of CT genotype had higher odds of GC when compared to CC genotype(OR=1.45,95%PI:1.08-1.95,P=0.01).Similar association was observed in a dominant model for INSR gene,where comparison of TT+CT vs CC genotypes showed an increased risk of GC(OR=1.44,95%PI:1.08-1.90,P=0.01).Other analyzed SNPs were not associated with the presence of GC.CONCLUSION INSR rs1051690 SNP is associated with increased risk of GC,while polymorphisms in IL12B,CCND1 and IL10genes are not linked with the presence of GC.