study of Helicobacter pylori duodenal ulcer promoting gene [cfupA] polymorphisms in Iraq and Turkey and their role in IL-12 secretion

The duodenal ulcer promoting gene [dupA] has been identified recently and was found to associate with duodenal ulceration in some populations and gastric cancer in others. It was also found that this gene is polymorphic and dupAl [but not dupAZ] substantially increased H. pylori-induced IL-12 production from mononuclear cells. The aims of this paper were to determine the prevalence ofdupA polymorphisms in Iraq and Turkey and their effect on major cytokine secretion from peripheral blood mononuclear cells [PBMCs]. We studied a total of 85 H. pylon strains: 42 [non-ulcer disease [MUD]: 26; duodenal ulcer [DU]: 13; gastric ulcer [GU]: 3; gastric cancer [GC]: 0] which were isolated from Iraq and 43 [NUD: 28; DU: 12; GU: 2; GC: 1] from Turkey. dupA was PCR amplified then polymorphisms were studied by sequencing 10 and 9 dupA+ Iraqi and Turkish strains, respectively. It was found that none of the Iraqi strains and [22%] of Turkish strains typed as dupA1. Finally, 2 dupA1, 4 dupA2 and 2 dupA-negative strains were assessed for their ability to induce IL-12, IL-10 and IL-8 in PBMCs. The IL-12 response of PBMCs cultured for 48 hours with wild-type strains carrying the dupAl was significantly higher [strain: mean +/- sd pg/ml, WTD1A:416 +/- 22.8; WTD1B:405.9 +/- 22.4] than those induced by wild-type H. pylori carrying the dupA2 [WTD2A:290.7 +/- 16.3; WTD2B:252.5 +/- 5; WTD2C:262.1 +/- 14; WTD2D:279.5 +/- 17; p<0.02 for all] and than those typed dupA-negative [WTD-veA:258.5 +/- 12; WTD-veB:225.6 +/- 32; p<0.02 for all] . Regarding IL-8 and IL-10, we found no significant differences between dupAl and others. These data suggested that dupAl is rare in these two countries and dupAl plays an important role in IL-12 secretion from PBMCs. More research is needed to determine the functionality ofdupA and its relationship with disease

[Study of the CagA gene prevalence in helicobacter pylori strains isolated from patients with upper gastrointestinal disorders in Iran]

Helicobacter pylori commonly is associated with gastritis: but only sometimes it causes clinically significant diseases such as gastric and duodenal ulcer. The development of disease depends on the virulence of the infecting H. pylori strain, the susceptibility of the host, and environment co-factors. The cytotoxin associated protein encoded by cagA gene is an important virulence factor that is produced by some H. pylori strains, and has been used as virulence marker in some populations. The aim of the study was to examine the prevalence of cagA gene in the isolated strains of H. pylori from patients with dyspeptic disease and to investigate the association of cagA gene and the severity of H. pylori related diseases in Iran. In this study, biopsy specimens were obtained from the antrum of 180 patients. After isolation of H. pylori and its DNA by standard methods, polymerase chain reaction [PCR] technique was used for detection of cagA bacterial gene. 92 out of the 180 patients had H. pylori strains. 70% were cagA gene positive. All patients with peptic ulcer [100%] and 44 out of 72 [61%] patients with non-ulcer dyspepsia were cagA positive [p<0.01]. There was significant difference in frequency of cagA gene in peptic ulcer disease and non-ulcer dyspepsia [p<0.01]. It showed that the risk of PUD in patients with cagA+ H. pylori infection may be higher than in those with cagA- H. pylori infection

Tissue Plasminogen Activator and Plasminogen Activator Inhibitor Type 1 Gene Polymorphism in Patients with Gastric Ulcer Complicated with Bleeding

Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) may be involved in the pathogenesis of peptic ulcers through suppression of fibrinolysis. This study was designed to investigate associations of t-PA and PAI-1 genes with clinical features of the patients with bleeding gastric ulcers. Eighty-four patients with peptic ulcers and 100 controls were studied between January 1998 and April 2000. We used polymerase chain reaction and endonuclease digestion to genotype for 4G/5G polymorphism in the promoter region of the PAI-1 gene and the Alurepeat insertion/deletion (I/D) polymorphism in intron h of the t-PA gene. Various clinical features, including lesion site, bleeding event, recurrence of ulcer, and rebleeding, were assessed using a multiple logistic regression model. The genotype distributions of both the t-PA and PAI-1 genes did not differ between the patient and control groups. The occurrence of the I/D or D/D genotype of t-PA was significantly higher in cases of duodenal ulcer (adjusted OR=4.39, 95% CI=1.12-17.21). When a dominant effect (i.e., 4G/4G or 4G/5G versus 5G/5G) of the 4G allele was assumed, the PAI-1 4G/4G genotype was independently associated with rebleeding after hemostasis (adjusted OR=5.07, 95% CI=1.03-24.87). Our data suggest that t-PA gene polymorphism is associated with duodenal ulcers, and that the PAI-1 gene may be a risk factor leading to recurrent bleeding after initial hemostasis.

Relevance of vacA Genotypes of Helicobacter pylori to cagA Status and Its Clinical Outcome

BACKGROUND: Determination of vacA mosaicism may be important because specific Helicobacter pylori vacA genotype can be used to predict different clinical outcome. The aim of this study was to assess the relationship of vacA genotypes of Helicobacter pylori to cagA status and its development of peptic ulcer diseases in Korean patients. METHODS: Gastric biopsy specimens were obtained from 53 patients with gastric ulcer(GU), 57 with duodenal ulcer (DU) and 26 with chronic gastritis(CG) patients; all patients were infected with Helicobacter pylori. Bacterial mRNAs in the gastric mucosa were amplified by RT-PCR, using synthetic oligonucleotide primers specific for the vacA and the cagA gene. Patients with vacA s1 subtype were further examined to determine whether they had s1a or s1b subtype. RESULTS: There was no correlation in frequency of vacA s1 and/or s1a genotype between CG and either GU or DU, as the vacA s1 and s1a/m1 were present in the majority of strains independent of clinical status(s1 ; 100.0% versus 94.3 % or 93.0 % and s1a/m1 ; 76.9% versus 62.3% or 64.9%, res pectively). Likewise, there was no difference in the prevalence of the cagA gene between CG and either GU or DU patients (92.3% versus 90.6% or 98.2%, respectively). In addition, the cagA-negative status did not predict the presence of vacA s2 genotype. CONCLUSION: These results strongly suggest that either cagA or vacA s1 and/or s1a is not proved to be a useful marker to distinguish disease-specific Helicobacter pylori strains for the development of peptic ulcer diseases in Korean patients.

Ulcera duodenal familiar y helicobacter pylori / Familiar duodenal ulcer and helicobacter pylori

Se describe un grupo familiar en el cual todos los integrantes que conviven en el mismo domicilio son portadores de gastritis y ulceras duodenales; en estos, se demuestra la colonización gástrica por helicobacter pylori (H.P.) cuyo tratamiento antimicrobiano logra, a la fecha, la erradicación del germen(H.P.), su asociación con la patología gastroduodenal, terapéutica y epidemiología. Al mismo se le atribuye el origen de la presente afección familiar y a su terapéutica exitosa la resolución de la patología

Niveles de pepsinógeno I sérico en descendientes de ulcerosos duodenales / Levels of blood pepsinogen I in the offspring of patients with duodenal ulcer

La hiperpepsinogenemia I es un fidedigno marcador subclínico de predisposición genética a sufrir úlcera duodenal, por ello determinamos los niveles basales de pepsinógeno I (PG I) sérico en 25 ulcerosos y el 75

Pepsinogênio I e úlcera duodenal / Serum pepsinogen I and duodenal ulcer

Neste artigo de revisäo procurou-se enfocar o papel do pepsinogênio/pepsina desde sua descoberta até sua aplicaçäo prática que, à semelhança do teste de secreçäo gástrica de ácido clorídrico, apresenta padröes diferentes de secreçäo basal ou estimulada na úlcera péptica, gastrite etc. Säo avaliados os métodos de determinaçäo do pepsinogênio, verificando-se que apesar da utilizaçäo do radioimunoensaio, outros métodos menos sofisticados, porém com alta especificidade, têm sido usados com sucesso. Os níveis séricos de pepsinogênio (NSP) após estímulo com Histalog discriminam pacientes com úlcera duodenal de indivíduos normais e säo mais elevados em homens do que em mulheres. É feito um paralelismo entre os pepsinogênios I e II verificando-se níveis mais elevados do pepsinogênio I em fumantes. O pepsinogênio I está aumentado na úlcera duodenal e o II na úlcera gástrica, e os dois tendem a caracterizar uma predisposiçäo genética para úlcera péptica. Finalmente, a principal aplicabilidade clínica da determinaçäo dos NSP do grupo I é na detecçäo da gastrite atrófica, em funçäo de seu potencial para o cáncer gástrico