Evidence for a major gene influencing 7-year increases in diastolic blood pressure with age

The contribution of genetic factors to blood pressure levels is well established. The contribution of genes to the longitudinal change in blood pressure has been less well studied, because of the lack of longitudinal family data. The present study investigated a possible major-gene effect on the observed increase with age in diastolic blood pressure (DBP) levels. Subjects included 965 unmedicated adults (age > or = 18 years) in 73 pedigrees collected in Utah as part of a longitudinal cardiovascular family study. Segregation analysis of DBP change over 7.2 years of follow-up identified a recessive major-gene effect with a gene frequency of p = .23. There was also a significant age effect on the genotypic means, which decreased expression of the major gene at older ages. For those inferred to have the genotype responsible for large DBP increases, DBP increased 32.3%, compared with a 1.5% increase in the nonsusceptible group (P < .0001). The relative risk of developing hypertension between the susceptible and nonsusceptible groups after 7.2 years was 2.4 (P = .006). Baseline DBP reactivities to mental arithmetic (P < .0001), and isometric handgrip (P < .0001) stress tests were greatest in those assigned to the susceptible genotype. We conclude that age-related changes in DBP are influenced by a major gene. Characteristics of this major-gene effect for greater age-related blood pressure increases include greater reactivity to mental and physical stressors. The present study thus provides evidence for genetic control of changes in blood pressure, in addition to the previously suggested genetic control of absolute blood pressure level.