Reciprocal interactions of obstructive sleep apnea and hypertension associated with ACE I/D polymorphism in males

Koyama, Renata G.; Drager, Luciano F.; Lorenzi-Filho, Geraldo; Cintra, Fátima D.; Pereira, Alexandre C.; Poyares, Dalva; Krieger, José Eduardo; Castro, Rosa M.R.P.S.; Tufik, Sérgio; de Mello, Marco Túlio; Pedrazzoli, Mario

doi:10.1016/j.sleep.2008.12.012

« Previous Next »Sleep Medicine
Volume 10, Issue 10 , Pages 1107-1111, December 2009

Reciprocal interactions of obstructive sleep apnea and hypertension associated with ACE I/D polymorphism in males

Renata G. Koyama
- Department of Psychobiology, Universidade Federal de São Paulo, Brazil
- Psychobiology and Exercise Research Center, Universidade Federal de São Paulo/UNIFESP, Rua Napoleão de Barros, 925, Vila Clementino, 04024-002 São Paulo, Brazil
Luciano F. Drager
- Hypertension Unit, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil
- Sleep Laboratory, Pulmonary Division, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil
Geraldo Lorenzi-Filho
- Sleep Laboratory, Pulmonary Division, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil
Fátima D. Cintra
- Department of Psychobiology, Universidade Federal de São Paulo, Brazil
Alexandre C. Pereira
- Hypertension Unit, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil
Dalva Poyares
- Department of Psychobiology, Universidade Federal de São Paulo, Brazil
José Eduardo Krieger
- Hypertension Unit, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil
Rosa M.R.P.S. Castro
- Department of Psychobiology, Universidade Federal de São Paulo, Brazil
Sérgio Tufik
- Department of Psychobiology, Universidade Federal de São Paulo, Brazil
Marco Túlio de Mello
- Department of Psychobiology, Universidade Federal de São Paulo, Brazil
- Psychobiology and Exercise Research Center, Universidade Federal de São Paulo/UNIFESP, Rua Napoleão de Barros, 925, Vila Clementino, 04024-002 São Paulo, Brazil
Mario Pedrazzoli
- Department of Psychobiology, Universidade Federal de São Paulo, Brazil
- Corresponding author. Tel.: +55 11 21490155/251; fax: +55 11 21490155.

Received 17 October 2008; received in revised form 17 December 2008; accepted 17 December 2008.

Abstract

Background

The angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism gene contributes to the genesis of hypertension (HTN) and may help explain the relationship between obstructive sleep apnea (OSA) and HTN. However, ACE is a pleiotropic gene that has several influences, including skeletal muscle and control of ventilation. We therefore tested the hypothesis that ACE polymorphism influences OSA severity.

Methods

Male OSA patients (apnea-hypopnea index [AHI]>5 events/h) from 2 university sleep centers were evaluated by polysomnography and ACE I/D polymorphism genotyping.

Results

We studied 266 males with OSA (age=48±13y, body mass index=29±5kg/m², AHI=34±25events/h). HTN was present in 114 patients (43%) who were older (p<0.01), heavier (p<0.05) and had more severe OSA (p<0.01). The I allele was associated with HTN in patients with mild to moderate OSA (p<0.01), but not in those with severe OSA. ACE I/D polymorphism was not associated with apnea severity among normotensive patients. In contrast, the only variables independently associated with OSA severity among patients with hypertension in multivariate analysis were BMI (OR=1.12) and II genotype (OR=0.27).

Conclusions

Our results indicate reciprocal interactions between OSA and HTN with ACE I/D polymorphism, suggesting that among hypertensive OSA males, the homozygous ACE I allele protects from severe OSA.

Keywords: Obstructive sleep apnea, Hypertension, ACE gene, ACE I/D polymorphism, Genetics, Gene–environment interaction