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Polymorphisms of genes encoding components of the sympathetic nervous system but not the renin–angiotensin system as risk factors for orthostatic hypotension

Tabara, Yasuharu; Kohara, Katsuhiko; Miki, Tetsuro

Original papers: Genetic aspects

Objective  The genetic background of orthostatic hypotension, an important risk factor for future cardiovascular morbidity and mortality, was investigated.

Design and methods  The study subjects comprised 415 community-dwelling individuals, who were free from any cardiovascular complications, aged 50 years or older (mean age 70.5 ± 9 years). Basal systolic blood pressure (SBP) was measured twice in supine posture after resting for more than 10 min. The orthostatic change in SBP was determined at 1 min and 3 min after standing up. The maximum change in SBP after standing was determined. Orthostatic hypotension was defined as a decline in SBP greater than 20 mmHg. The polymorphisms of genes encoding components of the renin–angiotensin system and sympathetic nervous system, which play pivotal roles in postural change in blood pressure regulation, were determined.

Results  There were no significant associations between the maximum change in SBP, the prevalence of orthostatic hypotension and gene polymorphisms of angiotensin-converting enzyme I/D, angiotensinogen M235T and angiotensin II type 1 receptor A1166C. On the contrary, polymorphism of the Gs protein α-subunit (GNAS1) T131C was significantly associated with the maximum change in SBP after standing [1.9 ± 16 versus −3.6 ± 16 mmHg (TT + TC versus CC), P = 0.008]. The prevalence of orthostatic hypotension was significantly different among GNAS1 genotypes (chi squared = 10.12, P = 0.011) and G-protein β3 subunit (GNB3) genotypes (chi squared = 6.12, P = 0.020). Multiple logistic regression analysis showed that both GNAS1 CC genotype [odds ratio (OR) = 2.79, 95% confidence interval (CI) 1.35–5.79, P = 0.006] and GNB3 C allele (OR = 1.78, 95% CI 1.06–3.00, P = 0.030) were independent risks for orthostatic hypotension.

Conclusions  These findings indicate that genes encoding sympathetic nervous components could be involved in the predisposition for orthostatic hypotension.

Department of Geriatric Medicine, Ehime University School of Medicine, Shigenobu-cho, Onsen-gun, Ehime, Japan.

Correspondence and requests for reprints to Dr Katsuhiko Kohara, Department of Geriatric Medicine, Ehime University School of Medicine, Shigenobu-cho, Onsen-gun, Ehime, 791-0295, Japan. Tel: +81 89 960 5851; fax: +81 89 960 5852; e-mail:

Received 26 October 2001

Revised 3 December 2001

Accepted 4 December 2001

© 2002 Lippincott Williams & Wilkins, Inc.