Association of tumor necrosis factor alpha gene polymorphisms with Helicobacter pylori infection in dyspeptic patients in Sri Lanka

Abstract

Single nucleotide polymorphisms present on the promoter sequence of the TNF-α gene may affect production of TNF-α, a pro-inflammatory cytokine, during immune responses. The presence of TNF-α polymorphisms is also reportedly associated with more severe manifestations of Helicobacter pylori infection. However, the frequency of TNF-α polymorphisms and the associated disease severity vary between different patient groups. In this study, gastric biopsies and blood specimens were collected from 138 patients with dyspepsia undergoing routine upper gastrointestinal endoscopy. Our institution's Ethics Review Committee approved the study and written informed consent was obtained from all participants. The presence of H. pylori was confirmed histologically in all patients. The frequency of TNF-α polymorphisms in the study cohort was investigated using PCR-restriction fragment length polymorphism and expression of serum TNF-α quantitated using a commercial ELISA assay. The proportions of selected TNF-α polymorphisms (TNF-α -238, -308 and -863) were similar in H. pylori-positive and -negative patients. Homozygous mutations of TNF-α polymorphisms were rarely detected in the study group. There was a significant difference in TNF-α concentrations between patients with mild chronic gastritis and TNF-α -308 GG genotype and patients with moderate to severe chronic gastritis (P = 0.008). It was not possible to identify an association between these genotypes and disease severity because of the low frequency of heterozygous and homozygous mutated genes in Sri Lankan patients with dyspepsia.

Contributing role of TNF, IL-10, sTNFR1 and TNF gene polymorphisms in disease severity of leptospirosis

“…In 2004, a study by Lingappa et al, found no significant association between TNF 308 gene polymorphism and leptospirosis [21]. In studies investigating the TNF gene polymorphisms among a group of dyspeptic patients and Dengue patients from Sri Lanka, a low frequency of heterozygous and mutated genotype was reported suggesting a predominance of the wild type genotype among Sri Lankans [13,22]. A similar observation of a low frequent of heterozygous and mutated TNF 238, 308 and 863 was noted by Mishra et al, among an Indian population during the course of pandemic Influenza [23].…”

“…Amplification was carried out in a 25 µl reaction mixture consisting of 1X buffer (Sigma Aldrich, USA) with 0.2 mM dNTPs (Promega), 0.2 µM of forward and reverse primer, 1.25 U of Taq polymerase (Sigma-Aldrich, USA) and 2 µl (~ 100 ng) of DNA. PCR amplification was performed in a thermal cycler (Flexigene Techne, UK) as described previously [13].…”

“…Amplified PCR product was subjected to RFLP using specific restriction enzymes [13]. Both PCR and RFLP products were visualized by agarose gel electrophoresis on a 1.5% agarose gel and 3% agarose gel, respectively, under UV transilluminator (VILBER LOURMAT Quantum ST4).…”

Variación en un solo nucleótido en genes de citocinas como marcadores de enfermedades

“…74 Arachchi y colaboradores encontraron una relación significativa de la SNV -308G/A FNT-α y la infección con el subtipo cag A de H. pylori en pacientes de Sri lanka. 75 Aunque no se ha encontrado relación de esta SNV con el cáncer gástrico, la SNV -238G/A se relaciona positivamente, específicamente el genotipo -238GG en poblaciones asiáticas. 76 Así mismo, Li y colaboradores encontraron que las SNV −238G/A y −308 G/A se relacionan con la susceptibilidad al cáncer de cérvix en habitantes de China.…”