Our results show that patients from the western region of Venezuela have an elevated prevalence of infection with H. pylori strains carrying known virulence genotypes with high genetic diversity. This highlights the importance of identifying gene variants for an early detection of virulent genotypes.

Uterine serpins (USs), designated as SERPINA14, are expressed in the endometrium in response to progesterone. All species identified as having USs exhibit epitheliochorial placentation and are in the Ruminantia and Suidae orders of the Laurasiatheria superorder. The objective was to identify US genes in species within and outside Laurasiatheria and evaluate whether evolution of the US gene was associated with development of the epitheliochorial placenta. Through queries of nucleotide and genomic databases, known US genes were identified (caprine, bovine, porcine, water buffalo), and new US coding sequences were found in dolphins, horses, dogs, and cats. The cat sequence contained several stop codons. No sequence was found in completed genomic sequences for primates, rodents, rabbits, opossums, or duck-billed platypuses. Reverse transcription-polymerase chain reaction confirmed expression of the US gene in the uterus of pregnant horses and dogs. The ratio of nonsynonymous/synonymous substitutions suggests that the US gene evolved under positive selection. In conclusion, the US gene evolved within the Laurasiatheria superorder to play a role in pregnancy for species with epitheliochorial placentation and some but not all Laurasiatheria species that have a different form of placentation. The positive selection taking place in the gene suggests development of species-specific functions.

Carriage of IL-1B +3954C allele and IL-1B-TCC (+) haplotype could favor colonization of bacterial cagAET (+) strains, and the combination of these bacterial and host haplotypes could play a synergistic role in development of premalignant gastric lesions. This work contributes to understanding of the complex interaction between H. pylori virulence factors and cytokine genotypes involved in gastrointestinal diseases.

Helicobacter pylori is a major cause of chronic gastritis (CG) and a firmly established carcinogen for gastric adenocarcinoma. However, the underlying pathogenic mechanisms are not fully understood. In this work we studied the association of the allelic variation of H. pylori-iceA virulence factor and human proinflammatory interleukin (IL)-1 polymorphisms (IL-1B-31, IL-1B-511, IL-1B+3954 and IL-1RN) with histopathological changes in the gastric mucosa of patients with CG in Venezuela, a country with a high incidence of and mortality from gastric cancer. Although in this work the iceA1 allele was found more frequently (69.7%), iceA2 allele prevalence was higher in samples with atrophic gastritis (AG) and more severe grades of granulocytic (G2/G3) [P=0.02; odds ratio (OR) 3.3] and lymphocytic infiltration (L2/L3). The carriage of iceA2 strains combined with proinflammatory IL-1 polymorphisms IL-1-31C or IL-1-511T allele carrier genotypes increased even more the risk of presenting G2/G3 with ORs of 5.1 and 5.4, respectively. Moreover, the iceA2/IL-1B-511T and iceA2/IL-1B-31C/-511T/IL-1RN(*)2 bacteria/host genotype combinations showed a significant association with AG and L2/L3, respectively. Despite not being well established, the bacterial risk factor iceA2 seems an important predictor of severe histological changes in CG, separately or in combination with host genetic factors in the Venezuelan population.

Background: Genetic predisposition may play a role in the prevalence of gastric cancer (GC). Aim: To investigate the relationship between selected interleukin-1 (IL-1) loci polymorphisms and gastric cancer risk in the Central-Western region of Venezuela, where gastric cancer represents the first cause of cancer-related deaths. Material and methods: In a case-control study, we compared the frequencies of IL-1B-511 and IL-1B+3954 biallelic polymorphism, and the pentallelic VNTR of IL-IRN in 84 gastric adenocarcinoma paraffin-embedded biopsies and 84 endoscopic biopsies from cancer-free controls. Results: No significant increase in genotypic frequencies in gastric cancer was observed for any of the IL-1B-511 allelic combinations. However, in a logistic regression analysis, a significant association emerged for the IL-1B+3954C carrier genotype (odds ratio (OR): 6.2; 95% confidence intervals (CI) 1.3-28.8). On the other hand, a significantly higher risk was evidenced for the IL-IRN*2/*2 genotype (OR: 7.0; 95% CI 2.3-21.5). Only patients with a well/moderately-differentiated adenocarcinoma that were homozygotes for the IL-IRN*2/*2 genotype, had a higher risk than the complete gastric cancer group (OR: 8.1, 95% CI 2.5-26.8). Some genotype combinations among IL-1B-511, IL-1B+3954 and IL-IRN showed an increased risk for developing gastric cancer and well/moderate differentiated adenocarcinoma, that was dependent of the presence of IL-IRN*2/*2 genotype. Conclusions: IL-IRN*2/*2 genotype is associated with increased risk of gastric cancer in the Venezuelan population (Rev Méd Chile 2009; 137: 63-70).