Effects of genetic variations in Acads gene on the risk of chronic obstructive pulmonary disease.

Abstract

Short-chain acyl-CoA dehydrogenase (SCAD), encoded by the Acads gene, functions in the mitochondrial β-oxidation of saturated short-chain fatty acids. SCAD deficiency results in mitochondrial dysfunction, which is one underlying biological mechanism of chronic obstructive pulmonary disease (COPD) pathogenesis. In this case-control study, we aimed to examine the effects of Acads gene polymorphisms on the susceptibility to COPD. A total of 16 tagging single-nucleotide polymorphisms (SNPs) in Acads gene region was identified and genotyped in 646 unrelated ethnic Chinese Han individuals including 279 patients with COPD and 367 healthy controls, their allelic and genotypic associations with COPD were determined by different genetic models. Furthermore, we estimated the linkage disequilibrium and haplotypes from these tested variants and determined the effects of haplotypes on the risk of COPD. The allelic and genotypic frequencies of SNPs rs2239686 and rs487915 in Acads gene were significantly different between COPD patients and controls, no statistically significant results were observed for other SNPs. Minor alleles A of rs2239686 and T of rs487915 were associated with a decreased pulmonary function and an increased COPD risk in a dominant manner. Functional analysis indicated that the risk allele A of rs2239686 could increase Acads expressions and the intracellular reactive oxygen species content. Haplotype analysis revealed that the haplotypes CTCCT in block 2 (rs3794216-rs3794215-rs34491494-rs558314-rs7312316) as well as GC in block 3 (rs2239686-rs487915) were protective against COPD, while haplotypes CTCGC in block 2 and AT in block 3 exhibited significant associations with the increased susceptibility to COPD. Our results suggest that Acads gene could potentially be a risk factor of COPD and thus its genetic variants might be as genetic biomarkers to predict the COPD susceptibility.

• Authors: Yiming Yuan, Shanshan Yang, Dan Deng, Yulong Chen, Caixia Zhang, Ruixue Zhou, Zhiguang Su
• Journal: IUBMB life (IUBMB Life) Vol. 72 Issue 9 Pg. 1986-1996 (09 2020) ISSN: 1521-6551 [Electronic] England
• PMID: 32593204 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 International Union of Biochemistry and Molecular Biology.

Chemical References

• Acyl-CoA Dehydrogenases

Topics

• Acyl-CoA Dehydrogenases (genetics)
• Case-Control Studies
• Female
• Genetic Predisposition to Disease
• Haplotypes
• Humans
• Male
• Phenotype
• Polymorphism, Single Nucleotide
• Pulmonary Disease, Chronic Obstructive (epidemiology, genetics, pathology)
• Risk Factors