Abstract
Large-scale genome-wide association analyses show an association between ADAMTS7 variations and coronary risk. However, the link between ADAMTS7 variability and ischaemic stroke (IS) has yet to be determined. This study evaluated ADAMTS7 variants with respect to the risk of IS. Genetic association analyses were performed in two independent case-control cohorts with 1279 patients with IS and 1268 age-matched healthy controls. Four variant genotypes of the ADAMTS7 gene were identified using the Multiplex SNaPshot assay. The rs3825807, rs11634042, and rs7173743 variants of ADAMTS7 were related to lower IS risk in both initial and replication cohort. The G-T-T-C and G-T-C-C haplotypes are significantly less prevalent in the IS group than in the control group. Further stratification according to IS subtypes indicated that carriers with the variant alleles of the rs3825807, rs11634042 and rs7173743 variants of ADAMTS7conferred a lower risk of developing large-artery atherosclerosis stroke subtype. Also, the mutated rs3825807 G allele, as well as the mutated rs11634042 T allele of ADAMTS7, are linked to a significant reduction of ADAMTS7 in patients with IS. Our findings confirm the role of ADAMTS7 in the pathophysiology of IS, with potentially significant implications for the prevention, treatment, and development of novel therapies for IS.
Highlights
Stroke is a leading cause of morbidity and mortality worldwide independent of socioeconomic conditions [1]
The rs3825807 G, rs11634042 T, and rs7173743 C alleles were linked with a lower risk of large-artery atherosclerosis (LAA)-subtype stroke after stratification analysis
Research has increasingly supported the role of A Disintegrin And Metalloproteinase with Thrombospondin 7 (ADAMTS7) as a promoter of neointimal proliferation, plaque development, and plaque calcification, as the underlying pathology for vast majority of ischaemic stroke (IS) patients
Summary
Stroke is a leading cause of morbidity and mortality worldwide independent of socioeconomic conditions [1]. Among all subtypes of stroke, 85% of deaths by stroke are attributed to ischaemic stroke (IS). This disease is promoted by multiple factors, such as genetics, hypertension, tobacco smoking, and diabetes [2]. The ADAMTS family includes 19 proteases with multiple domains, disintegrin, and metalloproteinase activity, all of which feature thrombospondin-like motifs. This family prominently intervenes in several pathophysiological phenomena, such as remodeling of the extracellular matrix (ECM), angiogenesis, hemostasis, organogenesis, arthritis, and cancer [3]. ADAMTS proteinases have been observed to promote atherosclerosis in recent research [3, 4]
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