Assessment of genetic risk factors for thoracic aortic aneurysm in hypertensive patients.
BACKGROUND
Conventional risk factors for thoracic aortic aneurysm including dissection (TAA) are thought to include age, arteriosclerosis, and hypertension. In addition, evidence suggests that genetic factors play a role in the development of this condition. The purpose of the present study was to identify genetic variants that confer susceptibility to TAA in hypertensive subjects.


METHODS
Study subjects comprised 1,351 hypertensive individuals: 88 patients with TAA and 1,263 subjects without this condition. The genotypes for 142 polymorphisms of 119 candidate genes were determined by a method that combines the PCR and sequence-specific oligonucleotide probes with suspension array technology.


RESULTS
Evaluation of genotype distributions by the chi2-test and subsequent multivariable logistic regression analysis with adjustment for covariates revealed that the 3949T-->G (3' untranslated region) polymorphism of the thrombospondin-2 gene (THBS2; odds ratio, 4.6), the -110A-->C polymorphism of the heat shock 70-kDa protein 8 gene (HSPA8; odds ratio, 0.4), the C-->T (Pro198Leu) polymorphism of the glutathione peroxidase 1 gene (GPX1; odds ratio, 0.3), the -6G-->A polymorphism of the angiotensinogen gene (AGT; odds ratio, 0.3), and the -850C-->T polymorphism of the tumor necrosis factor gene (TNF; odds ratio, 0.5) were significantly (P < 0.05) associated with TAA.


CONCLUSIONS
The variant allele of THBS2 is a risk factor for TAA in hypertensive patients, whereas the variant alleles of HSPA8, GPX1, AGT, and TNF are protective against this condition. Determination of genotypes for these polymorphisms may prove informative for assessment of the genetic risk for TAA.
Kato
Kimihiko
K
Department of Cardiovascular Medicine, Gifu Prefectural Government Tajimi Hospital, Tajimi, Japan. gogok@nifty.com
Oguri
Mitsutoshi
M
Kato
Noriyuki
N
Hibino
Takeshi
T
Yajima
Kazuhiro
K
Yoshida
Tetsuro
T
Metoki
Norifumi
N
Yoshida
Hidemi
H
Satoh
Kei
K
Watanabe
Sachiro
S
Yokoi
Kiyoshi
K
Murohara
Toyoaki
T
Yamada
Yoshiji
Y
D000368:Aged; D000784:Aortic Dissection / Q000235:genetics; D017545:Aortic Aneurysm, Thoracic / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000150:complications*; D008297:Male; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors
D015345:Oligonucleotide Probes