A variant of p22(phox), involved in generation of reactive oxygen species in the vessel wall, is associated with progression of coronary atherosclerosis

Carolyn Cahilly, Christie M. Ballantyne, Do-Sun Lim, Antonio Gotto, Ali J. Marian

Research output: Contribution to journalArticle

127 Citations (Scopus)

Abstract

A series of pro-oxidant and antioxidant enzymes, such as the NADPH oxidase system, maintain the redox state in the vessel wall. A major component of NADPH oxidase is p22(phox), which is implicated in atherosclerosis. We prospectively studied the association of the histidine (H)72→tyrosine (Y) mutation in p22(phox) with the severity and progression/regression of coronary artery disease (CAD), plasma lipid levels, clinical events, and response to treatment with fluvastatin in a well- characterized population. Genotypes were determined by polymerase chain reaction and restriction digestion with RsaI enzyme in 368 subjects in the Lipoprotein and Coronary Atherosclerosis Study (LCAS). Fasting plasma lipids and quantitative coronary angiograms were obtained at baseline and 2.5 years after randomization to fluvastatin or placebo. Subjects with CC genotype (n= 157) were identified by the presence of 396-bp and 113-bp products on gel electrophoresis. Those with TT (n=39) were identified by the presence of 316- bp, 113-bp, and 80-bp products, and those with CT (n=172) by the presence of 396-bp, 316-bp, 113-bp, and 80-bp products. Baseline and final plasma levels of lipids and the baseline severity of CAD were not significantly different among the genotypes. In the placebo group, subjects with the mutation had a 3- to 5-fold greater loss in mean minimum lumen diameter (MLD) (TT: - 0.15±0.15; CT: -0.17±0.26; and CC: -0.03±0.22 mm; P=0.006) and lesion- specific MLD (TT: -0.15±0.06; CT: -0.18±0.03; and CC: -0.06±0.03 mm; P=0.038) than those without. Progression was also more (TT: 8/17 [47%]; CT: 35/73 [48%]; and CC: 17/62 [27%]) and regression less (TT: 0/17 [0%]; CT: 1/73 [1%]; and CC: 11/72 [18%]) common in those with the mutation (P=0.002). The C242T mutation in p22(phox), involved in maintaining the redox state in the vessel wall, is associated with progression of coronary atherosclerosis in the LCAS population.

Original languageEnglish
Pages (from-to)391-395
Number of pages5
JournalCirculation Research
Volume86
Issue number4
Publication statusPublished - 2000 Mar 3
Externally publishedYes

Fingerprint

fluvastatin
Coronary Artery Disease
Reactive Oxygen Species
Mutation
NADPH Oxidase
Genotype
Lipids
Lipoproteins
Oxidation-Reduction
Placebos
Enzymes
Random Allocation
Histidine
Population
Electrophoresis
Digestion
Fasting
Atherosclerosis
Angiography
Antioxidants

Keywords

  • Atherosclerosis
  • Coronary disease
  • Genetics
  • Polymorphism
  • Reactive oxygen species

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

A variant of p22(phox), involved in generation of reactive oxygen species in the vessel wall, is associated with progression of coronary atherosclerosis. / Cahilly, Carolyn; Ballantyne, Christie M.; Lim, Do-Sun; Gotto, Antonio; Marian, Ali J.

In: Circulation Research, Vol. 86, No. 4, 03.03.2000, p. 391-395.

Research output: Contribution to journalArticle

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abstract = "A series of pro-oxidant and antioxidant enzymes, such as the NADPH oxidase system, maintain the redox state in the vessel wall. A major component of NADPH oxidase is p22(phox), which is implicated in atherosclerosis. We prospectively studied the association of the histidine (H)72→tyrosine (Y) mutation in p22(phox) with the severity and progression/regression of coronary artery disease (CAD), plasma lipid levels, clinical events, and response to treatment with fluvastatin in a well- characterized population. Genotypes were determined by polymerase chain reaction and restriction digestion with RsaI enzyme in 368 subjects in the Lipoprotein and Coronary Atherosclerosis Study (LCAS). Fasting plasma lipids and quantitative coronary angiograms were obtained at baseline and 2.5 years after randomization to fluvastatin or placebo. Subjects with CC genotype (n= 157) were identified by the presence of 396-bp and 113-bp products on gel electrophoresis. Those with TT (n=39) were identified by the presence of 316- bp, 113-bp, and 80-bp products, and those with CT (n=172) by the presence of 396-bp, 316-bp, 113-bp, and 80-bp products. Baseline and final plasma levels of lipids and the baseline severity of CAD were not significantly different among the genotypes. In the placebo group, subjects with the mutation had a 3- to 5-fold greater loss in mean minimum lumen diameter (MLD) (TT: - 0.15±0.15; CT: -0.17±0.26; and CC: -0.03±0.22 mm; P=0.006) and lesion- specific MLD (TT: -0.15±0.06; CT: -0.18±0.03; and CC: -0.06±0.03 mm; P=0.038) than those without. Progression was also more (TT: 8/17 [47{\%}]; CT: 35/73 [48{\%}]; and CC: 17/62 [27{\%}]) and regression less (TT: 0/17 [0{\%}]; CT: 1/73 [1{\%}]; and CC: 11/72 [18{\%}]) common in those with the mutation (P=0.002). The C242T mutation in p22(phox), involved in maintaining the redox state in the vessel wall, is associated with progression of coronary atherosclerosis in the LCAS population.",
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T1 - A variant of p22(phox), involved in generation of reactive oxygen species in the vessel wall, is associated with progression of coronary atherosclerosis

AU - Cahilly, Carolyn

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AU - Gotto, Antonio

AU - Marian, Ali J.

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N2 - A series of pro-oxidant and antioxidant enzymes, such as the NADPH oxidase system, maintain the redox state in the vessel wall. A major component of NADPH oxidase is p22(phox), which is implicated in atherosclerosis. We prospectively studied the association of the histidine (H)72→tyrosine (Y) mutation in p22(phox) with the severity and progression/regression of coronary artery disease (CAD), plasma lipid levels, clinical events, and response to treatment with fluvastatin in a well- characterized population. Genotypes were determined by polymerase chain reaction and restriction digestion with RsaI enzyme in 368 subjects in the Lipoprotein and Coronary Atherosclerosis Study (LCAS). Fasting plasma lipids and quantitative coronary angiograms were obtained at baseline and 2.5 years after randomization to fluvastatin or placebo. Subjects with CC genotype (n= 157) were identified by the presence of 396-bp and 113-bp products on gel electrophoresis. Those with TT (n=39) were identified by the presence of 316- bp, 113-bp, and 80-bp products, and those with CT (n=172) by the presence of 396-bp, 316-bp, 113-bp, and 80-bp products. Baseline and final plasma levels of lipids and the baseline severity of CAD were not significantly different among the genotypes. In the placebo group, subjects with the mutation had a 3- to 5-fold greater loss in mean minimum lumen diameter (MLD) (TT: - 0.15±0.15; CT: -0.17±0.26; and CC: -0.03±0.22 mm; P=0.006) and lesion- specific MLD (TT: -0.15±0.06; CT: -0.18±0.03; and CC: -0.06±0.03 mm; P=0.038) than those without. Progression was also more (TT: 8/17 [47%]; CT: 35/73 [48%]; and CC: 17/62 [27%]) and regression less (TT: 0/17 [0%]; CT: 1/73 [1%]; and CC: 11/72 [18%]) common in those with the mutation (P=0.002). The C242T mutation in p22(phox), involved in maintaining the redox state in the vessel wall, is associated with progression of coronary atherosclerosis in the LCAS population.

AB - A series of pro-oxidant and antioxidant enzymes, such as the NADPH oxidase system, maintain the redox state in the vessel wall. A major component of NADPH oxidase is p22(phox), which is implicated in atherosclerosis. We prospectively studied the association of the histidine (H)72→tyrosine (Y) mutation in p22(phox) with the severity and progression/regression of coronary artery disease (CAD), plasma lipid levels, clinical events, and response to treatment with fluvastatin in a well- characterized population. Genotypes were determined by polymerase chain reaction and restriction digestion with RsaI enzyme in 368 subjects in the Lipoprotein and Coronary Atherosclerosis Study (LCAS). Fasting plasma lipids and quantitative coronary angiograms were obtained at baseline and 2.5 years after randomization to fluvastatin or placebo. Subjects with CC genotype (n= 157) were identified by the presence of 396-bp and 113-bp products on gel electrophoresis. Those with TT (n=39) were identified by the presence of 316- bp, 113-bp, and 80-bp products, and those with CT (n=172) by the presence of 396-bp, 316-bp, 113-bp, and 80-bp products. Baseline and final plasma levels of lipids and the baseline severity of CAD were not significantly different among the genotypes. In the placebo group, subjects with the mutation had a 3- to 5-fold greater loss in mean minimum lumen diameter (MLD) (TT: - 0.15±0.15; CT: -0.17±0.26; and CC: -0.03±0.22 mm; P=0.006) and lesion- specific MLD (TT: -0.15±0.06; CT: -0.18±0.03; and CC: -0.06±0.03 mm; P=0.038) than those without. Progression was also more (TT: 8/17 [47%]; CT: 35/73 [48%]; and CC: 17/62 [27%]) and regression less (TT: 0/17 [0%]; CT: 1/73 [1%]; and CC: 11/72 [18%]) common in those with the mutation (P=0.002). The C242T mutation in p22(phox), involved in maintaining the redox state in the vessel wall, is associated with progression of coronary atherosclerosis in the LCAS population.

KW - Atherosclerosis

KW - Coronary disease

KW - Genetics

KW - Polymorphism

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