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Synonymous variant of TLR7 at restriction site rs864058 identified in Covid 19 Pakistani patients

机译:在 Covid 19 巴基斯坦患者中发现限制位点 rs864058 的 TLR7 同义变体

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摘要

Background: TLR7, the receptor accountable for immune response to RNA viruses, has been studied extensively to identify its variants related to the severity of Covid-19 in different populations worldwide. However, the genotype of Pakistani population is still unknown. This study aimed to determine the TLR7 genotypes and their relation with severity in our population. Methods: This cross sectional study collected data on 151 Covid-19 positive patients (aged 18-80 years), from June 2022 to May 2023, after an informed consent, from Ziauddin University and Hospital. Prior to that approval from ethics review committee was taken. The demographic variables and comorbidities were recorded along with health status till LAMA (Leave Against Medical Advise), recovery or death. The DNA was extracted from collected blood samples, PCR and Sanger sequencing was done for identification of TLR7 variants. SPSS was used for data analyses and Chi-Square for categorical variables. P-values of <0.05 was considered significant. Results: Out of 151 patients’ sequencing was done for 59 samples. The restriction site, rs864058 of TLR7 gene, identified G/A and G/G variants. This missense variant of TLR7 identified at rs864058 of TLR7 gene, has not been previously reported in population control databases. The genotype G/G was main variant of 49 (83%) patients, whereas, G/A was found in 10 (17%). Majority, 25 (51%) of patients with mild covid-19 had GG genotype but results were not significant (P=0.684). Among female patients the main genotype was GA 8 (80%) while male had G/G 29 (59.2%) with significant results (P=0.024). Since G/G genotype was the major genotype, high percentage was found in hypertensives [20 (40.8%)], Diabetics [13 (26.5%)], depression [24 (49%)] and pneumonia patients [20 (40.8%)]. However, significant association (P=0.023) was only found with pneumonia. Males, in majority had severe [17 (68%)] infection and death [40 (26.4%)], whereas, females had mild [14 (25%)] with [12 (7.9%)] deaths. Conclusion: A variant rs864058 “G/A” of TLR7, in relation to covid-19 were found in our population. Males were found more at risk of morbidity and mortality due to covid-19. Larger studies are required to further confirm these results.
机译:背景: TLR7 是负责对 RNA 病毒的免疫反应的受体,已被广泛研究以确定其在全球不同人群中与 Covid-19 严重程度相关的变体。然而,巴基斯坦人群的基因型仍然未知。本研究旨在确定我们人群中 TLR7 基因型及其与严重程度的关系。方法:这项横断面研究在获得知情同意后,从 2022 年 6 月至 2023 年 5 月从 Ziauddin 大学和医院收集了 151 名 Covid-19 阳性患者(18-80 岁)的数据。在此之前,已获得道德审查委员会的批准。人口统计变量和合并症与健康状况一起记录,直至 LAMA(违背医疗建议请假)、康复或死亡。从采集的血样中提取 DNA,进行 PCR 和 Sanger 测序以鉴定 TLR7 变体。SPSS 用于数据分析,卡方用于分类变量。<0.05 的 P 值被认为是显著的。结果: 在 151 例患者中,对 59 例样本进行了测序。限制性位点 TLR7 基因的 rs864058 鉴定了 G/A 和 G/G 变体。在 TLR7 基因的 rs864058 处鉴定的这种 TLR7 错义变体以前在种群对照数据库中没有报道过。基因型 G/G 是 49 例 (83%) 患者的主要变异,而 10 例 (17%) 患者发现 G/A。大多数 25 名 (51%) 轻度 covid-19 患者具有 GG 基因型,但结果不显著 (P=0.684)。在女性患者中,主要基因型为 GA 8 (80%),男性为 G/G 29 (59.2%),结果有统计学意义 (P=0.024)。由于 G/G 基因型是主要基因型,因此在高血压患者 [20 (40.8%)]、糖尿病患者 [13 (26.5%)]、抑郁症 [24 (49%)] 和肺炎患者 [20 (40.8%)] 中发现高百分比。然而,仅发现与肺炎有显著相关性 (P=0.023)。男性大多数患有重度 [17 (68%)] 感染和死亡 [40 (26.4%)],而女性患有轻度 [14 (25%)] 和 [12 (7.9%)] 死亡。结论:在我们的人群中发现了与 covid-19 相关的 TLR7 的变体 rs864058 “G/A”。发现男性因 covid-19 而发病和死亡的风险更高。需要更大规模的研究来进一步证实这些结果。

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