Department of Agricultural Science and Technology, Institute of Natural and Applied Sciences, Erciyes University, Kayseri 38039, Turkey.
Department of Neurosurgery, Ribat University Hospital, Khartoum 11111, Sudan.
World J Gastroenterol. 2022 Jan 14;28(2):242-262. doi: 10.3748/wjg.v28.i2.242.
() 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 () promoter region are considered a possible genetic basis for this disease.
To functionally characterize the genetic variations in the 5'-region (-584 to +107) of Sudanese patients infected with using in silico tools.
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 -1030 polymorphism was performed using PCR with confronting two-pair primer to investigate its association with the susceptibility to infection in the Sudanese population. Furthermore, Sanger sequencing was applied to detect single nucleotide polymorphisms in the 5'-region (-584 to +107) of in -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 -1030, sociodemographic characteristics and infection. Differences were statistically significant if < 0.05. Statistical analyses were performed using Stata version 11 software.
A total of seven single nucleotide polymorphisms were observed in the 5'-region of Sudanese patients infected with . 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 -1030 showed a lack of significant association between -1030T and susceptibility to and gastric cancer in the studied population ( = 0.1756) and ( = 0.8116), respectively. However, a significant association was detected between T/C genotype and infection (39.34% 19.67%, odds ratio = 2.69, 95% confidence interval: 1.17-6.17, = 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%).
Computational analysis was a valuable method for understanding gene expression patterns and guiding further and experimental validation.
幽门螺杆菌是一种普遍存在的细菌，它影响着全球近一半的人口，发病率和死亡率都很高。肿瘤坏死因子-α（TNF-α）启动子区域内的多态性被认为是该病的一个可能的遗传基础。
利用计算机工具对苏丹感染幽门螺杆菌患者的 5'-区域（-584 至+107）中的遗传变异进行功能特征描述。
在喀土穆州的主要公立和私立医院进行了一项观察性研究。共从接受内镜检查的患者中采集了 122 份胃活检组织。提取基因组 DNA。使用 PCR 与直面双引物对-1030 多态性进行基因分型，以研究其与苏丹人群中幽门螺杆菌感染易感性的关系。此外，应用 Sanger 测序检测感染患者 5'-区域（-584 至+107）中的单核苷酸多态性。使用 ECR 浏览器和多序列局部比对和可视化搜索引擎进行比较分析，对 11 个物种进行了可能的保守性分析。还构建了一个多变量逻辑回归模型，以估计-1030 与社会人口特征和幽门螺杆菌感染之间关联的优势比及其 95%置信区间。如果 < 0.05，则统计学差异显著。使用 Stata 版本 11 软件进行统计分析。
在感染幽门螺杆菌的苏丹患者的 5'-区域共观察到七个单核苷酸多态性。其中只有一个（T > A，-76）位于计算机预测的启动子区域（-146 至+10）内，并且预测会改变转录因子结合位点和复合调节元件。在 5'非翻译区检测到一个新的突变（A > T，+27），它可能影响转录后调控途径。-1030 基因分型显示，-1030T 与研究人群中幽门螺杆菌和胃癌的易感性之间无显著关联（=0.1756）和（=0.8116）。然而，T/C 基因型与幽门螺杆菌感染之间存在显著关联（39.34% 19.67%，比值比=2.69，95%置信区间：1.17-6.17，=0.020）。在黑猩猩（99.4%）、恒河猴（95.6%）、牛（91.8%）、家养犬（89.3%）、鼠（84.3%）、大鼠（82.4%）和负鼠（78%）中观察到（-146 至+10）区域的哺乳动物保守性。
计算分析是理解 基因表达模式和指导进一步 研究和实验验证的有价值的方法。
