Fibrillin-1 genotype and risk of prevalent hypertension: A study in two independent populations

Abstract

Objective. Mutations in the fibrillin-1 gene are the cause of Marfan syndrome. We wanted to investigate the relationship between a mutation in this gene and risk of prevalent hypertension. Methods. In a cross-sectional study, the effect of a G–A substitution in intron 27 in the fibrillin-1 gene (rs11856553) on risk of prevalent hypertension was studied in two large population-based studies: the Health 2006 study, consisting of 3193 women and men, age 18–69 years, and the MONICA10 study, consisting of 2408 women and men, age 41–72 years. In 1646 MONICA10 participants, blood pressure (BP) was also measured by 24-h ambulatory recordings. Results. Among the 3193 Health 2006 participants 23 had the G–A variant, and among the 2408 MONICA10 participants 18 had the G–A variant. In Health 2006, the odds ratio estimate (95% confidence intervals) for the G–A variant for risk of hypertension, defined as systolic (S) BP ≥ 140 mmHg or diastolic (D) BP ≥ 90 mmHg or on antihypertensive medicine, was 2.67 (1.14–6.18), p = 0.022. The corresponding figure for moderate to severe hypertension, defined as SBP ≥ 160 mmHg or DBP ≥ 100 mmHg, was 9.68 (4.24–22.12), p < 0.0001. In MONICA10, the odds ratio estimate (95% confidence intervals) for the G–A variant for risk of moderate to severe ambulatory hypertension, defined as 24-h mean SBP ≥ 150 mmHg or 24-h mean DBP ≥ 90 mmHg, was 5.73 (1.96–16.7), p = 0.0014. Conclusion. The G–A substitution in the fibrillin-1 gene (rs11856553) is a rare genetic variant that is associated with an increased risk of prevalent hypertension, particularly of moderate to severe prevalent hypertension.