title: Genetic variants rs1994016 and rs3825807 in ADAMTS7 affect its mRNA expression in atherosclerotic occlusive peripheral arterial disease.
abstract: OBJECTIVE
  Peripheral artery disease (PAD) is a vascular disease affecting peripheral circulation. Recently, genome-wide association studies revealed a relationship between single nucleotide polymorphisms (SNPs) in ADAMTS7 (a disintegrin and metalloprotease with thrombospondin motif 7) and atherosclerosis. In this study, we aimed to determine ADAMTS7 expression in peripheral blood mononuclear cells (PBMCs) and the frequency of ADAMTS7 rs1994016 and rs3825807 polymorphisms in a sample of Turkish patients with PAD, and to evaluate the association of matrix metalloproteinase (MMP) levels with PAD development.
  
  
  METHODS
  In this case-control study, ADAMTS7mRNA and protein expression was determined using reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and western blot, respectively, and rs1994016 and rs3825807 variants in ADAMTS7 were determined by real-time PCR in 115 PAD patients and 116 healthy controls. Plasma levels of nine MMPs were determined using a multiplex immunoassay system.
  
  
  RESULTS
  ADAMTS7mRNA levels were significantly higher in PAD patients than in controls (t=-2.75, P=.007). There was no significant difference in the frequencies of rs1994016 and rs3825807 between PAD patients and controls (P>.05). In PAD patients, ADAMTS7mRNA levels were significantly increased for the CC genotype of rs1994016 (t=-2.31, P=.026) and TT genotype of rs3825807 (t=-2.23, P=.032). Furthermore, plasma levels of MMP-1, MMP-3, MMP-7, MMP-10, MMP-12, and MMP-13 were significantly higher in PAD patients than in controls (P<.05).
  
  
  CONCLUSIONS
  This is the first report of the relationship between PAD and ADAMTS7 expression and the effects of the rs1994016 and rs3825807 variants on PAD development. ADAMTS7 may be associated with PAD development.
authors.affiliation: Department of Medical Biology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Burcu
authors.initials: B
authors.lastname: Bayoglu
authors.affiliation: Department of Cardiovascular Surgery, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Caner
authors.initials: C
authors.lastname: Arslan
authors.affiliation: Department of Cardiovascular Surgery, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Cigdem
authors.initials: C
authors.lastname: Tel
authors.affiliation: Department of Medical Biology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Turgut
authors.initials: T
authors.lastname: Ulutin
authors.affiliation: Department of Biostatistics and Medical Informatics, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Dirican
authors.affiliation: Department of Cardiovascular Surgery, Medical Faculty, Ondokuz Mayis University, Samsun, Turkey.
authors.forename: Serkan Burc
authors.initials: SB
authors.lastname: Deser
authors.affiliation: Department of Medical Biology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Mujgan
authors.initials: M
authors.lastname: Cengiz
mesh_terms: D000071118:ADAMTS7 Protein / Q000097:blood / Q000235:genetics / Q000378:metabolism; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000071118:ADAMTS7 Protein; C121534:ADAMTS7 protein, human
keywords: ADAMTS7; gene expression; matrix metalloproteinases; peripheral artery disease