Artikel
The C242T p22phox Genotype is associated with Intima Media Thickness
Der C242T p22phox Genotyp ist assoziiert mit Intima Media Dicke
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Autoren
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M. Schneider
- Medizinische Klinik IV/ Nephrologie, Krankenanstalten Gilead (Erlangen-Nürnberg, Bonn, Bielefeld, D)
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M. Ludwig
- Medizinische Klinik IV/ Nephrologie, Krankenanstalten Gilead (Erlangen-Nürnberg, Bonn, Bielefeld, D)
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Y. Huang
- Medizinische Klinik IV/ Nephrologie, Krankenanstalten Gilead (Erlangen-Nürnberg, Bonn, Bielefeld, D)
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M. Krekler
- Medizinische Klinik IV/ Nephrologie, Krankenanstalten Gilead (Erlangen-Nürnberg, Bonn, Bielefeld, D)
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K. Stumpe
- Medizinische Klinik IV/ Nephrologie, Krankenanstalten Gilead (Erlangen-Nürnberg, Bonn, Bielefeld, D)
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R. Schmieder
- Medizinische Klinik IV/ Nephrologie, Krankenanstalten Gilead (Erlangen-Nürnberg, Bonn, Bielefeld, D)
| Veröffentlicht: | 11. November 2004 |
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Gliederung
Text
Introduction
Intima-media-thickness (IMT) independently predicts future cardiovascular events in subjects with essential hypertension. The T allele of the C242T gene polymorphism of the p22phox subunit of the NADPH oxidase was recently linked to decreased vascular nitric oxide (NO) bioavailability. Since NO exerts various antiatherosclerotic effects, we hypothesized that this gene polymorphism may modulate the degree of IMT, in particular in early stages of atherosclerosis.
Methods
In the Cardiovascular Irbesartan Project (CVIP), a double blind randomized clinical study, patients with mild-to-moderate essential hypertension and increased IMT of the common carotid artery (CCA; 0.8-1.5 mm at the leading side) were treated with either irbesartan or atenolol for 18 months. The C242T genotype of the CYBA gene encoding the p22phox subunit of the NADPH oxidase was determined by a combined polymerase chain reaction-restriction digestion approach.
Results
Genotype distribution did not deviate from the Hardy-Weinberg equilibrium. Baseline parameters such as systolic and diastolic blood pressure were similar between genotypes. Subjects with the CC genotype (n=54) had lower IMT than subjects with the CT and TT genotype (N=60) (CCA mean: 0.80±0.01 vs 0.83±0.01 mm, p=0.03; Femoral artery: 0.66±0.17 vs 0.76±0.03 mm, p=0.02). Since C242T genotype did not influence the degree of regression of IMT by antihypertensive treatment, these differences persisted after 18 months treatment.
Conclusion
In subjects with arterial hypertension, the T allele of the C242T p22phox gene polymorphism is associated with a higher IMT of the CCA and the femoral artery. Thus, this gene polymorphism influences vascular structure, presumably by the modulation of NO bioavailability.
