Genetic Variants Associated with Chronic Obstructive Pulmonary Disease Risk: Cumulative Epidemiological Evidence from Meta-Analyses and Genome-Wide Association Studies

Abstract

Background. Last two decades, many association studies on genetic variants and chronic obstructive pulmonary disease (COPD) risk have been published. But results from different studies are inconsistent. Therefore, we performed this article to systematically evaluate results from previous meta-analyses and genome-wide association studies (GWASs). Material and Methods. Firstly, we retrieved meta-analyses in PubMed, Embase, and China National Knowledge Infrastructure and GWASs in PubMed and GWAS catalog on or before April 7th, 2022. Then, data were extracted and screened. Finally, two main methods—Venice criteria and false-positive report probability test—were used to evaluate significant associations. Results. As a result, eighty-eight meta-analyses and 5 GWASs were deemed eligible for inclusion. Fifty variants in 26 genes obtained from meta-analyses were significantly associated with COPD risk. Cumulative epidemiological evidence of an association was graded as strong for 10 variants in 8 genes (GSTM1, CHRNA, ADAM33, SP-D, TNF-α, VDBP, HMOX1, and HHIP), moderate for 6 variants in 5 genes (PI, GSTM1, ADAM33, TNF-α, and VDBP), and weak for 40 variants in 23 genes. Five variants in 4 genes showed convincing evidence of no association with COPD risk in meta-analyses. Additionally, 29 SNPs identified in GWASs were proved to be noteworthy based on the FPRP test. Conclusion. In summary, more than half (52.38%) of genetic variants reported in previous meta-analyses showed no association with COPD risk. However, 13 variants in 9 genes had moderate to strong evidence for an association. This article can serve as a useful reference for further studies.

Impact of Lung-Related Polygenic Risk Scores on Chronic Obstructive Pulmonary Disease Risk and Their Interaction with w-3 Fatty Acid Intake in Middle-Aged and Elderly Individuals

“…The present study identifies the potential genetic variants of the following genes: FAM13A, CHRNA, ADAM33, GSTM1, TNF-α, VDBP, HHIP, and HMOX1 [12]. These genes are involved in lung development, repair, and function, but their exact role in COPD is not yet fully understood.…”

“…Covariates: age, residence area, gender, BMI, job history in chemical and dust-related companies, smoking status, drinking status, total physical activity, and energy intake. The cutoff of each parameter: 1 100% of estimated energy requirement (EER), 2 70 energy percent (En%) of carbohydrates, 3 15 En% of protein, 4 15 En% of fat, 5 0.7 En% of w-3 fatty acid, 6 4.5 En% of w-3 fatty acid, 7 20 g/day of fiber, 8 75th percentile of each intake, 9 DRI of each nutrient (100 mg for V-C, 10 mg for V-E, 10 ug for V-D, and 50 ug for Se), 10 500 mg/day of Ca, 11 20 g/day of alcohol, 12 150 min/week of moderate exercise. *** Significantly different from the Health group.…”

“…Nutrients 2023, 15, x. https://doi.org/10.3390/xxxxx www.mdpi.com/journal/nutrients of fat, 5 0.7 En% of w-3 fatty acid, 6 4.5 En% of w-3 fatty acid, 7 20 g/day of fiber, 8 75th percentile of each intake, 9 DRI of each nutrient (100 mg for V-C, 10 mg for V-E, 10 ug for V-D, and 50 ug for Se), 10 500 mg/day of Ca, 11 20 g/day of alcohol, 12 150 min/week of moderate exercise. *** Significantly different from the Health group.…”

sRAGE levels are decreased in plasma and sputum of COPD secondary to biomass-burning smoke and tobacco smoking: Differences according to the rs3134940 AGER variant

“…The rs2071288 and rs2070600 have been previously associated with sRAGE levels [ 14 ], COPD risk [ 40 ], pulmonary function parameters [ 20 ], emphysema, and pulmonary fibrosis [ 41 ]. We did not observe any association for the rs2071288; however, the CT genotype of the rs2070600 was found to have a low COPD risk strongly influenced by age as a covariate.…”

Tumor necrosis factor‑α ‑308 G/A genetic polymorphism in patients with chronic obstructive pulmonary disease presenting with hyperactive airways

“…Two meta-analyses were previously conducted to investigate the association between the TNF-α -308 G/A (rs1800629) variant and COPD risk. One study revealed that this variant was significantly associated with COPD risk in the Asian population, but this association was no longer significant after adjusting for smoking (26). Another study showed that individuals with the G/G and G/A genotypes have a lower risk of developing COPD compared with A/A genotype carriers (27).…”