Khalid Beenish, Farukh Sadia, Kumar Ashokh, Baig Saeeda, Shahid Moazzam Ali
Department of Biochemistry, Hamdard University Karachi, Pakistan.
Department of Community Health Sciences, Aga Khan University Karachi, Pakistan.
Am J Blood Res. 2024 Aug 15;14(2):6-13. doi: 10.62347/YSKN6673. eCollection 2024.
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.
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. -values of <0.05 was considered significant.
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.
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.
Toll样受体7（TLR7）是负责对RNA病毒产生免疫反应的受体，已被广泛研究以确定其在全球不同人群中与新冠病毒疾病（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的基因型及其与疾病严重程度的关系。
这项横断面研究于2022年6月至2023年5月，在获得知情同意后，从齐亚乌丁大学和医院收集了151例Covid-19阳性患者（年龄在18 - 80岁之间）的数据。在此之前已获得伦理审查委员会的批准。记录了人口统计学变量和合并症以及直至患者自动出院（LAMA）、康复或死亡时的健康状况。从采集的血液样本中提取DNA，进行聚合酶链反应（PCR）和桑格测序以鉴定TLR7变体。使用社会科学统计软件包（SPSS）进行数据分析，分类变量采用卡方检验。P值<0.05被认为具有统计学意义。
在151例患者中，对59个样本进行了测序。TLR7基因的限制性位点rs864058鉴定出G/A和G/G变体。在TLR7基因rs864058处鉴定出的这种错义变体，在人群对照数据库中此前尚未见报道。基因型G/G是49例（83%）患者的主要变体，而G/A在10例（17%）患者中被发现。大多数（51%）轻症Covid-19患者具有GG基因型，但结果无统计学意义（P = 0.684）。在女性患者中主要基因型是GA（8例，80%），而男性患者中G/G基因型占29例（59.2%），结果具有统计学意义（P = 0.024）。由于G/G基因型是主要基因型，在高血压患者[20例（40.8%）]、糖尿病患者[13例（26.5%）]、抑郁症患者[24例（49%）]和肺炎患者[20例（40.8%）]中发现比例较高。然而，仅与肺炎存在显著关联（P = 0.023）。男性患者中大多数有重症感染[17例（68%）]和死亡[40例（26.4%）]，而女性患者病情较轻[14例（25%）]，死亡[12例（7.9%）]。
在我们的人群中发现TLR7的一个变体rs864058“G/A”与Covid-19相关。发现男性因Covid-19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。
