Ali Osman, Hussein
(2015)
Specific helicobacter pylori virulence and host genetic susceptibility factors: the potential role in gastroduodenal diseases.
Masters thesis, Universiti Sains Malaysia.
Abstract
Helicobacter pylori (H. pylori) is one of the most common human pathogens and
affects over 50% of the world population. H. pylori is associated with gastritis,
peptic ulcer, gastric cancer and gastric mucosa-associated lymphoid tissue
lymphoma. The interaction of several factors like environmental, bacterial virulence
and host genetic are believed to determine the severity and final outcome after H.
pylori infection. The aim of this study was to determine the distribution of H. pylori
virulence genes (cagA, babA2, SabAand dupA) and its correlation with clinical
outcomes. This study also assessed the pattern of H. pylori cagA EPIYA motifs,
EPIYA-A, -B, -C, or -D among different ethnic groups and its association with
gastroduodenal disease. The current study also explored the presence of SNPs as
genetic variants in the host genome which may be associated with susceptibility or
protection to H. pylori infection. This was a cross-sectional and case-control study
conducted between May 2012 to June 2014 among dyspeptic patients of different
ethnicities (Malay, Indian and Chinese) at the Endoscopy Unit of Hospital Universiti
Sains Malaysia and Hospital Kuala Lumpur. Genotyping of bacterial and host
genome was performed using PCR and Affymetrix SNP 6.0 microarray. This study
consists of 2 phases; in phase 1, a total of 105 patients who were confirmed positive
to have H. pylori infection were recruited into the study. The mean age and SD were
54.48 ±12.94 years and age range of 26 to 86 years old. Fifty seven (54.3%) of the
infected patients were males while forty eight (45.7%) were females. Based on the
endoscopic findings, 78 patients had gastritis, nine gastric ulcer, five duodenal ulcer
and 13 normal. The prevalence of H. pylori cagA, babA2, sabA and dupA genes in H.
pylori dyspeptic patients were 69.5%, 41.0%, 43.8% and 22.9% respectively. cagA
is more common in Indians (39.7%), babA2 is common in Malays (39.5%) and dupA
detection is more in Indian and Malay at the same rate (37.5%). The Chinese have
the lowest prevalence of the four genes. Majority of Chinese patients were
predominantly infected with cagA type A-B-D East Asian strain (88.9%) while cagA
type A-B-C Western strain (82.8%) was predominantly detected in the Indians while
the Malays have mixed strain. There were statistically significant difference
(P<0.001) between ethnicity and cagA EPIYA motifs, although we could not find
significant difference between H. pylori virulence genes and EPIYA types and
clinical outcomes. In phase II, a total of 80 (42 H. pylori positive and 38 H. pylori
negative) third generation patients with a mean age of 49.87 ± 12.335 years (age
range 20-75 years) were recruited. The present study identified SNPs rs3770521
(P=1.33 x 10-5) of XRCC5 gene, rs7042986 of SMARCA2 (P=0.0001) and
rs10860808 (P=0.0002) of DRAM1 gene as the susceptible SNPs to H. pylori
infection among the Indian, Malay and Chinese gastritis patients respectively. This
study also identified two protective SNPs rs1809578 (P=9.85x 10-6) of gene BANK1
and rs3776349 (P=0.0001) of gene ARHGAP26 among H. pylori the Indian and
Malay gastritis patients respectively. In conclusion, the lower prevalence of virulence
genes and variations among the different ethnic groups suggest that the bacterial
strains are geographically and ethnically dependent. No significant difference was
observed between virulence genes and clinical outcome. This study also shows that
EPIYA A-B-D and A-B-C are predominant in the Chinese and Indians respectively,
while the Malays have mixed strain. Finally, the current GWAS study revealed five
novel SNPs that may be associated with susceptibility and protection of H. pylori
gastritis in the three ethnic groups.
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