Cosegregation of blood pressure with a kallikrein gene family polymorphism.

Abstract

It has recently been proposed that sequence variation in the gene coding for tissue kallikrein might be involved in the pathogenesis of hypertension. However, molecular evidence of an association between a sequence alteration in the kallikrein gene family and the transmission of increased blood pressure has never been reported. In 32 recombinant inbred (RI) strains derived from the spontaneously hypertensive rat (SHR) and the normotensive Brown Norway rat (BN), we investigated whether a restriction fragment length polymorphism (RFLP) marking the kallikrein gene family cosegregated with blood pressure. In the RI strains that inherited the kallikrein RFLP from the SHR progenitor strain, the median systolic, diastolic, and mean arterial pressures were significantly greater than in the RI strains that inherited the kallikrein RFLP from the BN progenitor strain. These findings suggest that in the rat, sequence variation in the kallikrein gene family, or in closely linked genes, may have the capacity to affect blood pressure. (Hypertension 1991;17:242-246)

KLK1 A1789G gene polymorphism and the risk of coronary artery stenosis in the Chinese population

“…The A1789G (rs5517) polymorphism of the KLK1 gene exon 4 is a single-nucleotide substitution that causes the amino acid substitution Lys→Glu. Plasma Cr levels in patients with hypertension carrying the mutant allele G (AG or GG genotype) are significantly higher than those in patients carrying allele A (AA genotype) (Pravenec et al, 1991).…”

“…The genetic variant may influence urinary kallikrein activity and plasma creatinine (Cr) levels in Chinese subjects with hypertension (Pravenec et al, 1991). Recently, a significant association between the KLK1 A1789G polymorphism and hypertension was found in a large northern Han Chinese population (Berry et al, 1989;Hong et al, 2005).…”

The Kallikrein-Kinin System as a Regulator of Cardiovascular and Renal Function

“…Low urinary kallikrein excretion in children is one of the major genetic markers associated with a family history of essential hypertension, and children with high urinary kallikrein are less likely to be genetically predisposed to hypertension (264,289,304,321). A restriction fragment length polymorphism (RFLP) for the kallikrein gene family in SHR has been linked to high blood pressure (218), and urinary kallikrein excretion is decreased in several models of genetic hypertension. Urinary and/or arterial TK can also be decreased in renovascular hypertension and genetically hypertensive rats (43,47,52,124).…”

Relationship between the regulatory region polymorphism of human tissue kallikrein gene and essential hypertension

“…The polymorphisms of tissue kallikrein gene have been shown to be associated with blood pressure regulation in spontaneous hypertensive rats. 8 Transgenic mice overexpressing the human tissue kallikrein gene has been shown to exhibit a hypotensive phenotype. 9 Further, on the basis of studies of large Utah pedigrees, Berry et al 10 have suggested that a major gene effect accounts for one-half of the variance of the trait, with a dominant allele being associated with high urinary kallikrein activity and a reduced risk of hypertension.…”