Polymorphism of ADAMTS13 gene (Pro618Ala) in Thais and its association with coronary artery disease

Abstract

A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) is a metalloproteinase enzyme cleaving highly active ultralarge von Willebrand factor (vWF) multimers into the smaller size and less active vWF.  It has been shown in in vitro study that ADAMTS13 gene (Pro618Ala) polymorphism is associated with profound reduced ADAMTS13 activity. Thus, it has been hypothesized that low levels of ADAMTS13 may be a risk factor for arterial thrombosis and may influence coronary artery disease (CAD). This study therefore aims to investigate the frequency and association of ADAMTS13 Pro618Ala polymorphism with CAD in Thais. A total of 340 subjects were recruited in this study, 117 healthy controls and 223 patients who were clinically suspected of having CAD undergoing coronary angiography at Queen Sirikit Heart Center of the Northeast Hospital, Khon Kaen University. Based on angiographic results, 126 patients were classified as CAD and 97 patients were non-CAD. The ADAMTS13 P618A polymorphism was determined in genomic DNA extracted from leukocytes using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The frequencies of Pro and Ala allele in all subjects were 98.68 and 1.32 % respectively. The genotype frequencies of Pro/Pro and Pro/Ala in healthy controls, non-CAD and CAD were 98.29 vs. 1.71 %, 100 vs. 0 % and 94.44 vs. 5.56 %, respectively. Significant differences of genotype distributions of Pro/Ala were found in CAD compared to non-CAD group (P = 0.028). In conclusion, this study is the first report of the genotype distributions of the ADAMTS13 Pro618Ala polymorphism in Thais and suggested that it seems to be associated with coronary artery disease. However, due to a low frequency of the Ala allele in this population, a larger population should be required in further study.