ClinVar

In individuals heterozygous for a 230G-A transition in exon 3 of the KLKR gene, resulting in an arg53-to-his (R53H) substitution, Slim et al. (2002) identified a significant decrease in urinary kallikrein activity compared to controls (615953). This polymorphism was significantly more common in Afro-Caribbean individuals. Analysis of recombinant kallikrein variants revealed a major decrease in enzyme activity when arg53 was replaced by histidine, and a model of kallikrein derived from crystallographic data suggested that arg53 is involved in substrate binding.

In a study of 30 R53R homozygous and 10 R53H heterozygous young normotensive white males, Azizi et al. (2005) observed a 50 to 60% reduction in urinary kallikrein activity in R53H individuals, but renal and hormonal adaptation to dietary changes in sodium and potassium were unaffected. However, in studies of brachial artery function, R53H individuals consistently exhibited an increase in wall shear stress and a paradoxical reduction in artery diameter and lumen compared to R53R individuals. Azizi et al. (2005) concluded that this partial genetic deficiency in kallikrein activity is associated with a form of arterial dysfunction involving inappropriate inward remodeling of the brachial artery despite a chronic increase in shear stress.