title: Association of a matrix metallopeptidase 1 gene polymorphism with long-term             outcome of thoracic aortic aneurysm.
abstract: Although genetic variants are thought to contribute to the development of thoracic aortic aneurysm including dissection (TAA), it remains unclear whether gene polymorphisms are associated with the long-term outcome of TAA. The purpose of the present study was to identify genetic variants associated with the long-term outcome of medically treated patients with TAA. A total of 103 medically-treated patients with TAA (13 aneurysms and 90 dissections) were retrospectively studied for their outcomes (mean follow-up period, 24 months). The genotypes for 95 polymorphisms of 89 candidate genes were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Evaluation of genotype distributions by the Chi-square test and subsequent multivariable logistic regression analysis with adjustment for covariates revealed that the -340A→G polymorphism (rs514921) of the matrix metallopeptidase 1 gene (MMP1) was significantly (P=0.0288) associated with the outcome of TAA, with the minor G allele being related to a favorable outcome. The aneurysm diameter was significantly (P=0.0167) smaller in the combined group of the AG and GG genotypes for this polymorphism than in subjects with the AA genotype. Kaplan-Meier survival curves constructed according to MMP1 genotypes showed a more favorable outcome of TAA (log-rank P=0.0146) in subjects with the G allele of rs514921. Determination of genotype for this polymorphism may prove informative for assessment of the long-term outcome of TAA.
authors.affiliation: Meitoh Hospital, Nagoya, Japan. gogok@nifty.com
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Kato
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Tokuda
authors.forename: Naohiko
authors.initials: N
authors.lastname: Inagaki
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Yoshida
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Fujimaki
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Oguri
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hibino
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yokoi
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
authors.forename: Yoshiji
authors.initials: Y
authors.lastname: Yamada
mesh_terms: D000368:Aged; D017545:Aortic Aneurysm, Thoracic / Q000201:enzymology / Q000235:genetics*; D019540:Area Under Curve; D016009:Chi-Square Distribution; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007564:Japan; D053208:Kaplan-Meier Estimate; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D012372:ROC Curve; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1