MGST3 – Chronic Obstructive Pulmonary Disease

MGST3 has emerged as a significant gene in the context of chronic obstructive pulmonary disease (COPD), with recent multi‑patient studies demonstrating a robust association between genetic variation in this gene and COPD risk, particularly in patients exposed to biomass‑burning smoke (BBS) and tobacco smoke (PMID:36825998). This association is supported by data from large cohorts that evaluated SNP profiles in xenobiotic‐processing enzymes and reported that MGST3 contributes to the overall genetic architecture of COPD.

The genetic evidence comes from two independent studies. In one study, a cohort of 1500 subjects was assessed and multiple SNPs in xenobiotic metabolism genes—including MGST3—were found to be significantly associated with COPD secondary to BBS (PMID:36825998). A second study focusing on antioxidant enzymes in European American and African American populations also reported significant associations; notably, the SNP rs2297765 in MGST3 was linked to an attenuated decline in lung function among smokers (PMID:23688726).

Although no specific coding HGVS variant has been provided in these reports, the association derives from population‐based SNP studies rather than traditional family‐based segregation of rare coding alleles. Therefore, the curated variant list for MGST3 remains empty, as the evidence implicates common regulatory or coding variation not captured by a singular pathogenic HGVS string.

Family segregation data are not applicable in these genome‑wide association designs; however, the replicated gene‑level association across independent cohorts lends additional weight to the overall evidence. In both studies, no extended family data were presented, and the focus remained on population statistics.

Limited functional data have been provided regarding MGST3. While direct in vivo or in vitro functional assays are not described in the supplied literature, the gene’s known involvement in xenobiotic metabolism and oxidative stress pathways is biologically plausible given the pathophysiology of COPD. This functional rationale supports the genetic association by suggesting that altered MGST3 activity may influence the detoxification of inhaled pollutants.

In summary, the genetic association between MGST3 and COPD is well supported by multi‑patient studies with replication across diverse populations. Although specific HGVS variants have not been delineated, the combined genetic and limited functional evidence offers a clinically actionable insight. Key take‑home message: MGST3 is a promising molecular marker that may improve diagnostic decision‑making and risk stratification in COPD.

References

• Current issues in molecular biology • 2023 • SNPs Sets in Codifying Genes for Xenobiotics-Processing Enzymes Are Associated with COPD Secondary to Biomass‑Burning Smoke PMID:36825998
• Free radical biology & medicine • 2013 • Genetic variation in antioxidant enzymes, cigarette smoking, and longitudinal change in lung function PMID:23688726

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