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Smoking attenuates cardioprotective effects linked to allelic variation at ADAMTS7

15 Jul 2017

Smoking could weaken the genetic protection against coronary heart disease (CHD), with a recent study demonstrating that allelic variation at rs7178051 associated with reduced ADAMTS7 expression provides stronger CHD protection in never-smokers than in ever-smokers.

Exposure of human coronary artery smooth muscle cells to cigarette smoke extract particularly leads to increased vascular ADAMTS7 expression.

Researchers analysed genetic variants at 45 loci previously reported to be associated with CHD risk in a cohort of 60,919 CHD patients and 80,243 controls from 29 gene-smoking interaction studies. Five loci linked to smoking behaviour were also evaluated. A fixed-effects meta-analysis was performed to calculate and pool study-specific gene-smoking interaction effects.

A novel gene-smoking interaction was identified for a variant upstream of the ADAMTS7 gene. Every T allele of rs7178051 reduced the risk of CHD by 12 percent in never-smokers (p=1.3×10–16) and by only 5 percent in ever-smokers (p=2.5×10–4). The difference reflected a 60-percent loss of CHD protection conferred by the allelic variation in individuals who smoked tobacco (p=8.7×10–5 for interaction).

Moreover, the protective T allele at rs7178051 was associated with a reduction in ADAMTS7 expression in human aortic endothelial cells and lymphoblastoid cell lines. Exposure of human coronary artery smooth muscle cells to cigarette smoke extract resulted in an induction of ADAMTS7.

The present data have mechanistic and clinical implications, providing novel insights into the potential mechanisms of CHD in cigarette smokers and pointing towards the directional impact of the ADAMTS7 locus on CHD, researchers noted.

A member of the ADAMTS family of secreted zinc metalloproteases, the ADAMTS7 (A disintegrin and metalloproteinase with thrombospondin motifs-7) has been shown to modulate vascular smooth muscle cell phenotype switching and migration and that this may be mediated via the putative ADAMTS7 substrates expressed in vascular tissue. [PLoS One 2013;8:e71954; Circulation 2015;131:1202-1213; Am J Hum Genet 2013;92:366-374; Circ Res 2009;104:688-698]

“Inhibition of ADAMTS7 is a novel potential therapeutic strategy for CHD that may have particular benefits in individuals who smoke cigarettes,” researchers said.

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Most Read Articles
2 days ago
Overall survival (OS) and head and neck cancer (HNC)-specific survival vary among HNC sites, according to a study. In particular, cigarette smoking is a prognostic factor of OS and HNC-specific survival in patients with cancer of the oral cavity and oropharynx, whereas alcohol consumption is a prognostic factor of both survival outcomes in patients with cancer of the larynx.
18 Sep 2017
The additional use of intermittent low-energy diet (LED) or daily meal replacements after a mean 10-percent weight loss and 1-year maintenance effectively maintains weight loss in obese patients with knee osteoarthritis for 3 years, according to a recent study.
3 days ago
Adiponectin, but not leptin, is significantly correlated with proteinuria and its severity in systemic lupus erythematosus (SLE) nephritis, reveals a new cross-sectional study.
Jairia Dela Cruz, 3 days ago
Laparoscopic sleeve gastrectomy (SG) appears to be effective in Asians, with early weight loss correlating with midterm weight maintenance and remission of obesity-related comorbidities 1 year after the surgery, according to a study.