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.

Associative analysis of multi-omics data indicates that acetylation modification is widely involved in cigarette smoke-induced chronic obstructive pulmonary disease

“…These studies showed that ECMs were involved in the process of COPD, but whether it was related to their acetylation difference needs to be investigated further. Acyl-CoA dehydrogenase short chain (ACADS) may be a risk factor for COPD ( 53 ). Short chain acyl-CoA dehydrogenase (SCAD) is encoded by ACADS, and ACADS gene variants cause the mutation of SCAD, leading to mitochondrial damage and excessive production of reactive oxygen species (ROS) ( 54 , 55 ).…”