Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, Thailand.
Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, Thailand.
Infect Genet Evol. 2021 Mar;88:104682. doi: 10.1016/j.meegid.2020.104682. Epub 2020 Dec 16.
The reported association between an insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene and the risk for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) remains controversial despite the publication of four meta-analyses on this topic. Here, we updated the meta-analysis with more studies and additional assessments that include adults and children within the context of the coronavirus disease 2019 (COVID-19) pandemic.
Sixteen articles (22 studies) were included. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using three genetic models (allele, recessive and dominant), in which ARDS patients were compared with non-ARDS patients (A1) and healthy controls (A2). Mortality outcomes were also assessed (A3). The influence of covariates was examined by meta-regression. Bonferroni correction was performed for multiple pooled associations. Subgroup analyses based on ethnicity (Asians, Caucasians) and life stage (adults, children) were conducted. Heterogeneity was addressed with outlier treatment.
This meta-analysis generated 68 comparisons, 21 of which were significant. Of the 21, four A1 and three A3 highly significant (P = 0.00001-0.0008) outcomes withstood Bonferroni correction. For A1, allele and recessive associations were found in overall (OR 0.49, 95% CI 0.39-0.61), Caucasians (OR 0.46, 95% CI 0.35-0.61) and children (ORs 0.49-0.66, 95% CI 0.33-0.84) analyses. For A3, associations were found in overall (dominant: OR 0.45, 95% CI 0.29-0.68) and Asian subgroup (allele/ dominant: ORs 0.31-0.39, 95% CIs 0.18-0.63) analyses. These outcomes were either robust, or statistically powered or both and uninfluenced by covariates.
Significant associations of the ACE I/D polymorphism with the risk of ALI/ARDS were indicated in Caucasians and children as well as in Asians in mortality analysis. These findings were underpinned by high significance, high statistical power and robustness. ACE genotypes may be useful for ALI/ARDS therapy for patients with COVID-19.
尽管已有四项关于血管紧张素转换酶（ACE）基因插入/缺失（I/D）多态性与急性肺损伤（ALI）/急性呼吸窘迫综合征（ARDS）风险之间关联的荟萃分析发表，但该关联仍存在争议。在这里，我们更新了荟萃分析，纳入了更多的研究，并进行了包括成人和儿童在内的 COVID-19 大流行背景下的附加评估。
纳入了 16 篇文章（22 项研究）。使用三种遗传模型（等位基因、隐性和显性）比较 ARDS 患者与非 ARDS 患者（A1）和健康对照（A2），估计比值比（OR）和 95%置信区间（CI）。还评估了死亡率结局（A3）。通过荟萃回归检查协变量的影响。对多个合并关联进行了 Bonferroni 校正。根据种族（亚洲人、高加索人）和生命阶段（成人、儿童）进行亚组分析。使用异常值处理解决异质性问题。
本荟萃分析共产生了 68 次比较，其中 21 次具有统计学意义。在这 21 次中，有 4 次 A1 和 3 次 A3 的结果具有高度显著性（P=0.00001-0.0008），经 Bonferroni 校正后仍然具有统计学意义。对于 A1，等位基因和隐性关联在总体（OR 0.49，95%CI 0.39-0.61）、高加索人（OR 0.46，95%CI 0.35-0.61）和儿童（ORs 0.49-0.66，95%CI 0.33-0.84）分析中均有发现。对于 A3，在总体（显性：OR 0.45，95%CI 0.29-0.68）和亚洲亚组（等位基因/显性：ORs 0.31-0.39，95%CI 0.18-0.63）分析中也有发现关联。这些结果要么稳健，要么具有统计学意义，要么两者兼而有之，不受协变量的影响。
ACE I/D 多态性与 ALI/ARDS 风险之间的关联在高加索人和儿童以及亚洲人的死亡率分析中具有统计学意义。这些发现基于高显著性、高统计学效能和稳健性。ACE 基因型可能对 COVID-19 患者的 ALI/ARDS 治疗有用。
