Hereditary intermediate phenotypes in African American hypertension

Abstract

Promising intermediate phenotypes, which may be useful for studies in African American families, include baroreceptor sensitivity to low and high pressure stimuli, cold pressor test responses, and biochemical markers such as plasma chromogranin A, dopamine-beta-hydroxylase and urinary kallikrein excretion. Identification of genes involved in complex traits such as hypertension may be facilitated by the intermediate phenotype approach, combined with recent advances in quantitative genetics and linkage mapping. Further studies are needed to pinpoint the nature of genes in African American hypertension.

Renal kallikrein excretion: role of ethnicity, gender, environment, and genetic risk of hypertension

“…3 Because kallikrein excretion may also mark the risk of development of hypertension and because the prevalence of hypertension varies widely across ethnic strata, 1,[12][13][14][15]18 we sought to understand how ethnicity, 11 environment, 19 gender, 10,11 and genetic risk of hypertension 4 interact to influence renal kallikrein excretion. In particular, we studied three ethnic groups from widely differing geographic sites of ancestry (Europe, sub-Saharan Africa, and east Asia), since previous reports on kallikrein excretion have not directly compared more than two such groups.…”

“…In particular, we studied three ethnic groups from widely differing geographic sites of ancestry (Europe, sub-Saharan Africa, and east Asia), since previous reports on kallikrein excretion have not directly compared more than two such groups. 1,8,9,11,20 Reports over the past two decades have demonstrated substantial ethnic differences in renal kallikrein excretion, 2,6-9 with African-Americans displaying consistently lower kallikrein activity than Caucasians. Here we found a substantial diminution in urinary kallikrein excretion in African-Americans (Table 1; F = 5.3, P = 0.006), but no difference (P = 1.0) between Caucasian and Asian values.…”

“…16,24 We have previously shown hypertension family history to influence such potentially pathogenic traits as baroreceptor slope 24 or the cardiac response to alpha 2 -adrenergic blockade. 16 Such early phenotypic responses, occurring in at-risk subjects even before the onset of hypertension, may qualify as more informative 'intermediate phenotypes' 1,2,16 in the genetic analysis of this complex trait. In this sample, heterogeneity of kallikrein distributions (Figure 2 (histogram)) corresponded to hypertension family history (chi-square = 29.6, P Ͻ 0.001), with the lower kallikrein strata enriched in family history positives (P = 0.048).…”

“…1 Investigations have shown that more than one gene is responsible for essential hypertension, though the specific genes remain elusive. 2 'Intermediate phenotypes' 1 are traits associated with essential hypertension with such advantageous properties as earlier penetrance, superior heritability, or logicial involvement in the pathogenesis of the disease; such phenotypes may be valuable in profiling at-risk individuals for future development of the ultimate disease trait.…”

“…1 The hypotensive property of human urine, now known as kallikrein, has been described since 1909. 3 However, the relationships between urinary kallikrein and hypertension have only more recently been elucidated, over the last 30 years.…”