: Genetic variations of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) and von Willebrand factor (vWF) were related to ADAMTS13 levels. Reduction of ADAMTS13 activity may affect atherosclerotic progression. However, the associations of polymorphisms of these genes with coronary artery disease (CAD) are still unclear. This study, therefore, aimed to investigate the relationship of genetic variations and haplotypes of ADAMTS13 and vWF with CAD risk in Thais. A case-control study was performed in 197 CAD and 135 non-CAD patients. Genetic polymorphisms of ADAMTS13 (P475S, Q448E, rs2073932, P618A, A900V, S903L, rs652600, and rs4962153) and vWF (V1565L and Y1584C) along with ADAMTS13 activity, vWF antigen and vWF activity were examined in the patients. The vWF V1565L polymorphism was associated with increased ADAMTS13 activity, whereas none of ADAMTS13 polymorphisms or haplotypes was associated with its activity. Interestingly, haplotype analysis indicated that the QAGA or H4 haplotype of ADAMTS13 gene had a protective effect on CAD after adjustment for ABO blood group [odds ratio (OR) = 0.3, 95% confidence interval (CI) = 0.1, 0.6] and major CAD risk factors (OR = 0.3, 95% CI = 0.1, 0.7). However, the combination of H4 haplotype and the L allele of V1565L was not associated with increased ADAMTS13 activity when compared with the V allele. ADAMTS13 haplotype had an independent protective effect on CAD and genetic variation of vWF V1565L polymorphism modulates ADAMTS13 activity.
Background:The imbalance of von Willebrand factor (vWF) and a disintegrin and metalloproteinase with a thrombospondin type 1 motif member 13 (ADAMTS13) has been associated with atherosclerosis progression. A high level of vWF which regulates thrombus formation is associated with diabetes mellitus (DM), and some ADAMTS13 and vWF polymorphisms have effects on their levels. Therefore, this study aimed to evaluate the associations of ADAMTS13 and vWF polymorphisms and their levels with DM and severity of coronary stenosis.Materials and Methods:Eighty-seven DM and 84 control individuals were recruited. vWF and ADAMTS13 activities as well as vWF antigen were measured by collagen-binding assay (CBA), residual-CBA, and in-house enzyme-linked immunosorbent assay, respectively. ADAMTS13 and vWF polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism.Results:The E and G alleles and AA genotype of ADAMTS13 Q448E, rs2073932, and rs652600, respectively, were independently associated with DM (odds ratio [OR] [95% confidence interval (CI)] = 2.5 [1.1, 5.6], 2.3 [1.0, 5.2], and 4.7 [1.2, 18.6], respectively). Moreover, E allele and AA genotype of Q448E and rs652600 were also significantly associated with multi-vessel disease (OR [95% CI] = 2.2 [1.0, 4.8] and 3.2 [1.0, 10.0], respectively), while the E and G allele of Q448E and rs2073932 were associated with high Gensini score (OR [95% CI] = 2.3 [1.1, 4.9] and 2.3 [1.1, 5.1], respectively).Conclusion:Association of ADAMTS13 polymorphisms with DM, number of vessel stenosis, and Gensini score may indicate the possible contribution of ADAMTS13 polymorphisms to atherosclerosis progression and severity of coronary stenosis in DM.
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