title: Protective effect of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 haplotype on coronary artery disease.
abstract: : 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.
authors.affiliation: aBiomedical Sciences Program, Graduate School bCardiovascular Research Group cFaculty of Associated Medical Sciences, Department of Clinical Microscopy dFaculty of Associated Medical Sciences, Department of Clinical Chemistry eFaculty of Medicine, Department of Pathology fFaculty of Medicine, Department of Physiology gQueen Sirikit Heart Center of the Northeast hFaculty of Medicine, Department of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Supakanya
authors.initials: S
authors.lastname: Lasom
authors.forename: Nantarat
authors.initials: N
authors.lastname: Komanasin
authors.forename: Nongnuch
authors.initials: N
authors.lastname: Settasatian
authors.forename: Chatri
authors.initials: C
authors.lastname: Settasatian
authors.forename: Upa
authors.initials: U
authors.lastname: Kukongviriyapan
authors.forename: Pongsak
authors.initials: P
authors.lastname: Intharapetch
authors.forename: Vichai
authors.initials: V
authors.lastname: Senthong
mesh_terms: D000071120:ADAMTS13 Protein / Q000235:genetics* / Q000378:metabolism; D020816:Amino Acid Motifs; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000517:prevention & control*; D019483:Disintegrins / Q000502:physiology*; D005260:Female; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008297:Male; D045726:Metalloproteases / Q000502:physiology*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D020011:Protective Agents / Q000494:pharmacology; D019700:Thrombospondin 1 / Q000235:genetics; D014841:von Willebrand Factor / Q000235:genetics*
chemical_list: D019483:Disintegrins; D020011:Protective Agents; D019700:Thrombospondin 1; D014841:von Willebrand Factor; D045726:Metalloproteases; D000071120:ADAMTS13 Protein