Human Genetics

, Volume 110, Issue 1, pp 89–94

Paraoxonase gene Gln192Arg (Q192R) polymorphism is associated with coronary artery spasm

  • Teruhiko Ito
  • Hirofumi Yasue
  • Michihiro Yoshimura
  • Shota Nakamura
  • Masafumi Nakayama
  • Yukio Shimasaki
  • Eisaku Harada
  • Yuji Mizuno
  • Hiroaki Kawano
  • Hisao Ogawa
Original Investigation

Abstract.

We recently reported that oxidative stress is involved in the pathogenesis of coronary spasm. We hypothesized that oxidative-stress-related genetic factors and certain polymorphisms in the paraoxonase gene (PON1) and platelet-activating factor acetylhydrolase (PAF-AH) might influence the pathogenesis of coronary spasm. We therefore examined the possible association between the PON1 Q192R or PAF-AH V279F polymorphisms and coronary spasm in 214 patients with coronary spasm and 212 control subjects. Genotypes were determined by polymerase chain reaction/restriction fragment length polymorphism analysis. The incidence of the PON1-192R allele was significantly higher in the coronary spasm group than in the control group (65% vs 53%; P=0.0005). The PAF-AH-279F allele was not associated with coronary spasm (15% vs 16%; P=0.8781). Multiple logistic regression analysis with forward stepwise selection involving the PON1-192R allele and the environmental risk factors revealed that the most predictive independent risk factor for coronary spasm was the PON1-192R allele (significance=0.0016, OR=2.52), followed by cigarette smoking (significance=0.0007, OR=2.01). We also measured plasma levels of TBARS (thiobarbituric acid-reactive substances) as a marker of oxidative stress. TBARS levels were higher in R/R types than in Q/Q types (2.115±0.086 nmol/ml [n=25] vs 1.676±0.102 nmol/ml [n=11], P<0.01). Thus, there is a significant association between the PON1-192R allele and coronary spasm; the PON1-192R allele may play an important role in the genesis of coronary spasm, probably by attenuating the suppression of oxidative stress.

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Copyright information

© Springer-Verlag 2001

Authors and Affiliations

  • Teruhiko Ito
    • 1
  • Hirofumi Yasue
    • 2
  • Michihiro Yoshimura
    • 1
  • Shota Nakamura
    • 1
  • Masafumi Nakayama
    • 1
  • Yukio Shimasaki
    • 1
  • Eisaku Harada
    • 1
  • Yuji Mizuno
    • 2
  • Hiroaki Kawano
    • 1
  • Hisao Ogawa
    • 1
  1. 1.Department of Cardiovascular Medicine, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto 860-8556, JapanJapan
  2. 2.Kumamoto Aging Research Institute, 6-8-1 Yamamuro, Kumamoto 860-8518, JapanJapan

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