title: ADAMTS7 locus confers high cross-race risk for development of coronary atheromatous plaque.
abstract: Genome-wide association studies of coronary artery disease (CAD) have recently identified a new susceptibility locus, ADAMTS7, in subjects of European ancestry. However, the significance of this locus in Chinese populations has not been identified. Therefore, this study was designed to evaluate the effect of rs3825807, a non-synonymous variant in the prodomain of the ADAMTS7 protease, on CAD risk and atherosclerosis severity in a Chinese population. We performed genetic association analyses in two independent case-control cohorts, which included a total of 8154 participants. Additionally, the association between the ADAMTS7 rs3825807 genotype and the proportion of CAD patients with 3- and 1-vessel disease was tested. We found that ADAMTS7 rs3825807 was associated with susceptibility to CAD in a Chinese population [odds ratio (OR) = 1.15, 95 % confidence interval (CI) = 1.05-1.26, P = 0.002]. The association remained significant after adjusting for clinical covariates (adjusted OR = 1.12, 95 % CI = 1.02-1.24, P = 0.02). Among 3741 angiographically documented CAD patients, the rs3825807 risk allele showed a significant association with disease severity (P = 0.04, trend P = 0.02). Additionally, 3-vessel disease demonstrated a strong and direct association with ADAMTS7 rs3825807 gene dosage (P = 0.02). Overall, our findings indicate that the significant associations observed between this coding variant in ADAMTS7 and the risk of CAD development are cross-ethnic, and the gene dosage is consistent with the degree of coronary atheromatous burden.
authors.affiliation: Division of Cardiology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.
authors.forename: Ling
authors.initials: L
authors.lastname: You
authors.affiliation: Department of Internal Medicine and Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Lun
authors.initials: L
authors.lastname: Tan
authors.affiliation: Department of Internal Medicine and Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Internal Medicine and Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Rufei
authors.initials: R
authors.lastname: Shen
authors.affiliation: Department of Internal Medicine and Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Sandip
authors.initials: S
authors.lastname: Chaugai
authors.affiliation: Department of Internal Medicine and Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China. dwwang@tjh.tjmu.edu.cn.
authors.forename: Dao Wen
authors.identifier: http://orcid.org/0000-0002-1877-1634
authors.initials: DW
authors.lastname: Wang
authors.affiliation: Division of Cardiology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China. cuiwei@medmail.com.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Cui
mesh_terms: D051722:ADAM Proteins / Q000235:genetics*; D000071118:ADAMTS7 Protein; D000483:Alleles; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D012307:Risk Factors
chemical_list: D051722:ADAM Proteins; D000071118:ADAMTS7 Protein; C121534:ADAMTS7 protein, human
keywords: ADAMTS7; Atherosclerosis severity; Coronary artery disease