Abstract
Tissue kallikrein is an enzyme involved in the release of kinin in peripheral tissues. It is believed to regulate hemodynamics and electrolyte transport in the kidney. The present study analyzed polymorphisms of tissue kallikrein in Japanese volunteers and examined the associations between allele H in the promoter region, which has been shown to have decreased promoter activity, and urinary kallikrein activity and physiological parameters in subjects on an ad libitum diet. Ninety and 73 volunteers were analyzed for the promoter and coding regions of the tissue kallikrein gene, respectively. The allelic frequency of allele H was found to be 24%. One synonymous and three non-synonymous polymorphisms were found in the coding regions. Urinary kallikrein activity was not significantly decreased in subjects with allele H compared to those without allele H, although they were low in two homozygotes of allele H. Urinary excretions of calcium and sodium were larger in the subjects with allele H than in those without. It is concluded that allele H is a common polymorphism in Japanese and may contribute to decreased reabsorptions of calcium and sodium in the kidney. Further interventional studies are needed to clarify the phenotype of allele H with respect to renal electrolyte handling.
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Acknowledgements
This study was supported by the 35th research grant from the Japan Research Foundation for Clinical Pharmacology. We would like to acknowledge the medical staff of the Clinical Trial Center of Kitasato University East Hospital for their assistance with conducting the human study, and Stephen McKay, MSc, of McKay MedPharm & Associates for his assistance with editing the manuscript.
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Fujita, T., Yasuda, S., Kamata, M. et al. A common polymorphism in the tissue kallikrein gene is associated with increased urinary excretions of calcium and sodium in Japanese volunteers. J Hum Genet 58, 758–761 (2013). https://doi.org/10.1038/jhg.2013.93
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DOI: https://doi.org/10.1038/jhg.2013.93
