Association of a matrix metallopeptidase 1 gene polymorphism with long-term outcome of thoracic aortic aneurysm

作者：Kato Kimihiko^*; Tokuda Yoshiyuki; Inagaki Naohiko; Yoshida Tetsuro; Fujimaki Tetsuo; Oguri Mitsutoshi; Hibino Takeshi; Yokoi Kiyoshi; Murohara Toyoaki; Yamada Yoshiji

来源：International Journal of Molecular Medicine, 2012, 29(1): 125-132.

DOI：10.3892/ijmm.2011.804

• aortic aneurysm
• genetics
• polymorphism
• matrix metallopeptidase 1
• outcome

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 -%26gt; 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.

• 出版日期2012-1