Allelic Variation of Gene and Its Association with Gastric Pathologies in Clinical Samples Collected in Jordan.

is a well-established causative agent of gastritis, peptic ulcers, gastric adenocarcinoma, and primary gastric lymphoma. It colonizes the human stomach and expresses numerous virulent factors that influence disease progression. Among these factors is the cytotoxin gene, which encodes the vacuolating capacity of the cytotoxin and plays a key role in the bacterium's pathogenic potential. This study investigated the allelic diversity of the among strains infecting patients in Jordan with various gastric conditions and examined potential associations between genotypes, histopathological and endoscopic findings, and the development of gastric diseases. Gastric biopsies were collected from 106 patients at two hospitals in Jordan who underwent endoscopic examination. The collected biopsies for each patient were subjected to histopathological assessment, urease detection using the Rapid Urease Test (RUT), a diagnostic test for , and molecular detection of the gene and its s and m alleles. The histopathology reports indicated that 83 of 106 patients exhibited gastric disorders, of which 81 samples showed features associated with infection. The RUT was positive in 76 of 106 with an accuracy of 93.8%. Real-time polymerase chain reaction (RT-PCR) targeting the 16S rRNA gene confirmed the presence of in 79 of 81 histologically diagnosed cases as infected (97.5%), while the gene was detected only in 75 samples (~95%). To explore genetic diversity, PCR-amplified fragments underwent sequence analysis of the gene. The m-allele was detected in 58 samples (73%), the s-allele was detected in 45 (57%), while both alleles were not detected in 13% of samples. The predominant genotype combination among Jordanians was s2/m2 (50%), significantly linked to mild chronic gastritis, followed by s1/m2 (35%) and s1/m1 (11.8%) which are linked to severe gastric conditions including malignancies. Age-and gender-related differences in genotype were observed with less virulent s2m2 and s1m2 genotypes predominating in younger adults specially males, while the more virulent m1 genotypes were found exclusively in females and middle-aged patients. Genomic sequencing revealed extensive diversity within , likely reflecting its long-standing co-evolution with human hosts in Jordan. This genetic variability plays a key role in modulating virulence and influencing clinical outcomes. Comprehensive characterization of genotypic variations through whole-genome sequencing is essential to enhance diagnostic precision, strengthen epidemiological surveillance, and inform targeted therapeutic strategies. While this study highlights the significance of the and alleles, future research is recommended in order to investigate the other allelic variations, such as the i, d, and c alleles, to achieve a more comprehensive understanding of pathogenicity and associated disease severity across different strains. These investigations will be crucial for improving diagnostic accuracy and guiding the development of targeted therapeutic strategies.