Genomics and Molecular Medicine Unit, Council of Scientific and Industrial Research (CSIR) - Institute of Genomics and Integrative Biology (IGIB), New Delhi 110007, India; Department of Biotechnology, Delhi Technological University, Shahbad Daulatpur, Delhi, India.
Genomics and Molecular Medicine Unit, Council of Scientific and Industrial Research (CSIR) - Institute of Genomics and Integrative Biology (IGIB), New Delhi 110007, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
Infect Genet Evol. 2022 Aug;102:105299. doi: 10.1016/j.meegid.2022.105299. Epub 2022 May 8.
Pneumonia, an acute respiratory tract infection, is one of the major causes of mortality worldwide. Depending on the site of acquisition, pneumonia can be community acquired pneumonia (CAP) or nosocomial pneumonia (NP). The risk of pneumonia, is partially driven by host genetics. CYP1A1 is a widely studied pulmonary CYP family gene primarily expressed in peripheral airway epithelium. The CYP1A1 genetic variants, included in this study, alter the gene activity and are known to contribute in lung inflammation, which may cause pneumonia pathogenesis. In this study, we performed a meta-analysis to establish the possible contribution of CYP1A1 gene, and its three variants (rs2606345, rs1048943 and rs4646903) towards the genetic etiology of pneumonia risk. Using PRISMA guidelines, we systematically reviewed and meta-analysed case-control studies, evaluating risk of pneumonia in patients carrying the risk alleles of CYP1A1 variants. Heterogeneity across the studies was evaluated using I2 statistics. Based on heterogeneity, a random-effect (using maximum likelihood) or fixed-effect (using inverse variance) model was applied to estimate the effect size. Pooled odds ratio (OR) was calculated to estimate the overall effect of the risk allele association with pneumonia susceptibility. Egger's regression test and funnel plot were used to assess publication bias. Subgroup analysis was performed based on pneumonia type (CAP and NP), population, as well as age group. A total of ten articles were identified as eligible studies, which included 3049 cases and 2249 healthy controls. The meta-analysis findings revealed CYP1A1 variants, rs2606345 [T vs G; OR = 1.12 (0.75-1.50); p = 0.02; I2 = 84.89%], and rs1048943 [G vs T; OR = 1.19 (0.76-1.61); p = 0.02; I2 = 0.00%] as risk markers whereas rs4646903 showed no statistical significance for susceptibility to pneumonia. On subgroup analysis, both the genetic variants showed significant association with CAP but not with NP. We additionally performed a spatial analysis to identify the key factors possibly explaining the variability across countries in the prevalence of the coronavirus disease 2019 (COVID-19), a viral pneumonia. We observed a significant association between the risk allele of rs2606345 and rs1048943, with a higher COVID-19 prevalence worldwide, providing us important links in understanding the variability in COVID-19 prevalence.
肺炎是一种急性呼吸道感染，是全球主要的死亡原因之一。根据感染部位的不同，肺炎可以分为社区获得性肺炎（CAP）或医院获得性肺炎（NP）。肺炎的风险部分取决于宿主遗传学。CYP1A1 是一个广泛研究的肺 CYP 家族基因，主要在周围气道上皮细胞中表达。本研究纳入的 CYP1A1 基因变体改变了基因活性，并已知与肺部炎症有关，这可能导致肺炎的发病机制。在这项研究中，我们进行了荟萃分析，以确定 CYP1A1 基因及其三个变体（rs2606345、rs1048943 和 rs4646903）在肺炎风险的遗传病因中的可能作用。我们使用 PRISMA 指南系统地回顾和荟萃分析了评估携带 CYP1A1 变体风险等位基因的患者患肺炎风险的病例对照研究。使用 I2 统计量评估研究间的异质性。根据异质性，应用随机效应（使用最大似然法）或固定效应（使用倒数方差法）模型来估计效应大小。计算合并优势比（OR）以估计风险等位基因与肺炎易感性相关的总体效应。使用 Egger 回归检验和漏斗图评估发表偏倚。根据肺炎类型（CAP 和 NP）、人群和年龄组进行亚组分析。共确定了 10 篇符合条件的研究文章，其中包括 3049 例病例和 2249 例健康对照。荟萃分析结果显示，CYP1A1 变体 rs2606345[T 对 G；OR=1.12（0.75-1.50）；p=0.02；I2=84.89%]和 rs1048943[G 对 T；OR=1.19（0.76-1.61）；p=0.02；I2=0.00%]是肺炎易感性的风险标志物，而 rs4646903 与肺炎易感性无统计学意义。在亚组分析中，这两个遗传变异都与 CAP 显著相关，但与 NP 无关。我们还进行了空间分析，以确定可能解释 2019 年冠状病毒病（COVID-19），即病毒性肺炎在全球流行率差异的关键因素。我们观察到 rs2606345 和 rs1048943 的风险等位基因与全球更高的 COVID-19 流行率之间存在显著关联，这为我们理解 COVID-19 流行率的差异提供了重要线索。
