Identification of functional tumor necrosis factor-alpha promoter variants associated with Helicobacter pylori infection in the Sudanese population: Computational approach.

BACKGROUND: Helicobacter pylori (H. pylori) is a ubiquitous bacterium that affects nearly half of the world's population with a high morbidity and mortality rate. Polymorphisms within the tumor necrosis factor-alpha (TNF-A) promoter region are considered a possible genetic basis for this disease. AIM: To functionally characterize the genetic variations in the TNF-A 5'-region (-584 to +107) of Sudanese patients infected with H. pylori using in silico tools. METHODS: An observational study was carried out in major public and private hospitals in Khartoum state. A total of 122 gastric biopsies were taken from patients who had been referred for endoscopy. Genomic DNA was extracted. Genotyping of the TNF-A-1030 polymorphism was performed using PCR with confronting two-pair primer to investigate its association with the susceptibility to H. pylori infection in the Sudanese population. Furthermore, Sanger sequencing was applied to detect single nucleotide polymorphisms in the 5'-region (-584 to +107) of TNF-A in H. pylori-infected patients. Bioinformatics analyses were used to predict whether these mutations would alter transcription factor binding sites or composite regulatory elements in this region. A comparative profiling analysis was conducted in 11 species using the ECR browser and multiple-sequence local alignment and visualization search engine to investigate the possible conservation. Also, a multivariate logistic regression model was constructed to estimate odds ratios and their 95% confidence intervals for the association between TNF-A-1030, sociodemographic characteristics and H. pylori infection. Differences were statistically significant if P < 0.05. Statistical analyses were performed using Stata version 11 software. RESULTS: A total of seven single nucleotide polymorphisms were observed in the TNF-A 5'-region of Sudanese patients infected with H. pylori. Only one of them (T > A, -76) was located at the in silico-predicted promoter region (-146 to +10), and it was predicted to alter transcription factor binding sites and composite regulatory elements. A novel mutation (A > T, +27) was detected in the 5' untranslated region, and it could affect the post-transcriptional regulatory pathways. Genotyping of TNF-A-1030 showed a lack of significant association between -1030T and susceptibility to H. pylori and gastric cancer in the studied population (P = 0.1756) and (P = 0.8116), respectively. However, a significant association was detected between T/C genotype and H. pylori infection (39.34% vs 19.67%, odds ratio = 2.69, 95% confidence interval: 1.17-6.17, P = 0.020). Mammalian conservation was observed for the (-146 to +10) region in chimpanzee (99.4%), rhesus monkey (95.6%), cow (91.8%), domesticated dog (89.3%), mouse (84.3%), rat (82.4%) and opossum (78%). CONCLUSION: Computational analysis was a valuable method for understanding TNF-A gene expression patterns and guiding further in vitro and in vivo experimental validation.

Knowledge gaps of STIs in Africa; Systematic review.

Sexually Transmitted Infections (STIs) are ambiguous burden of tremendous health, social and economic consequences. The current systematic review was conducted in order to determine awareness and knowledge of Africans toward sexually transmitted infections, not only concerning HIV/AIDS, but also other STIs such as gonorrhea, syphilis, HBV, HCV and HPV. A systematic review of literature was conducted, studies were retrieved and selected after fulfilling the inclusion criteria as well as passing the assessment procedure. Related data was extracted, quantitative analysis was conducted among participants who responded to questions related to HIV, HBV, HCV, HPV or STIs knowledge, sensitivity analysis as well as subgroup analysis were also conducted. Seventy four articles addressing knowledge among 35 African countries were included and 136 questions were analyzed and synthesized. The question "does using condom reduces HIV transmission?" was answered by 1,316,873 Africans in 35 countries, 66.8% [95% Cl; 62.6, 70.9] answered yes. While the question "is sexual contact a possible route of HBV transmission?" was answered by 7,490 participants in 5 countries; 42.5% [95% Cl; 20.4, 64.7] answered yes. The differences observed among populations are highlighting the possibility for improvement by directing light toward specific populations as well as addressing specific awareness knowledge to ensure that the general as well as the related specific preventive knowledge is improved.