Helicobacter pylori (Hp) is causally linked with gastric
pre-malignant lesions, gastric cancer (GCA) and peptic ulcer disease (PUD). In
Africa, PUD is prevalent while GCA has reportedly low incidence. Less is known
about pre-malignant lesions. Hp genes cagA and vacA are
established virulence factors and have been associated with increased
gastroduodenal disease (GDD) risk. Further, diversity in the Carboxyl-terminus
of cagA can influence GCA risk. Virulence studies have evolved from
candidate-based to more robust genome wide association studies (GWAS). Here, a
clinical and histopathological assessment of GDD in West Africa was performed,
as well as an evaluation of associated Hp genetic variation.
In 136 dyspeptic patients from
Ghana, pre-malignant lesions had low prevalence, 14.7%, most of which were
located distally. vacA and cagA Hp strains were identified by PCR
in 69.2% and 74.8% of 159 dyspeptic Ghanaian patients respectively; cagA-(internal
duplication region) being more prevalent than cagA-(hydrophilic region).
Duodenal ulcer was associated with cagA-(hydrophilic region) and vacAs1m1.
Multi-locus sequence typing
(MLST) of seven housekeeping genes have previously identified multiple distinct
H. pylori populations or lineages such as hpAfrica1 and hpEurope. An
agnostic analysis of Hp virulence employed a GWAS using 193 controls
from the European-African admixed population of Cape Verde (CV) and 101 cases
from reference databases. African controls and cases clustered within
hpAfrica1, while European controls and cases clustered within hpEurope. Genes
significant for GCA or PUD were established virulence factors cagPAI, vacA
and babA2. Prominent among these were lipopolysaccharide and
peptidoglycan biosynthesis proteins. Phylogenetic analyses showed a cluster of
closely related CV lineages that diverged from European cases. This CV_outgroup
was notable for absence of major virulence genes.
Although
several novel and established variants have been linked to GDD, population
structure in bacteria can lead to false positives in linkage dysequilibrium
(LD) with genuine risk variants. Hence, validation studies are required to
assist in risk stratification of infected individuals for further management.
Ultimately, GDD risk is multi-factorial. Therefore, studies ought to evaluate
host, bacterial and environmental factors in an integrated design.</p