Ethnic and age-specific acute lung injury/acute respiratory distress syndrome risk associated with angiotensin-converting enzyme insertion/deletion polymorphisms, implications for COVID-19: A meta-analysis

Abstract

Background

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.

Methods

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.

Results

This meta-analysis generated 68 comparisons, 21 of which were significant. Of the 21, four A1 and three A3 highly significant (P ^a = 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.

Conclusions

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.

Highlights

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  Acute respiratory distress syndrome (ARDS) is a likely endpoint for patients with severe COVID-19 infection.

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  Genetic variation of patients may help predict ARDS outcomes.

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  This meta-analysis clarified associations between ACE I/D polymorphisms and ARDS.

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  Caucasians and children were more susceptible to ARDS than Asians and adults.

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  Risk of death due to ARDS impacted Asians more than Caucasians.

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  ACE genotypes may be useful in ARDS therapy for COVID-19-afflicted patients.