Abstract

In humans, genome-wide association studies have identified variants in the uromodulin gene (UMOD) associated with blood pressure and renal function. This study aimed to evaluate the association of single nucleotide polymorphisms at the UMOD locus with renal function and blood pressure in cats. We retrospectively identified cats aged 14 years that had participated in a geriatric monitoring program, and from which stored DNA samples were available, from a computerised database. We then measured the association of specific single nucleotide polymorphisms in the feline UMOD gene with renal function and systolic blood pressure as continuous variables and, also, the dichotomous outcome of azotaemic chronic kidney disease and systemic hypertension. Eight intronic single nucleotide polymorphisms, one 1372 base pairs upstream from UMOD and two exonic single nucleotide polymorphisms were evaluated in 227 cats with renal and blood pressure data. An analysis of 188 cats found four single nucleotide polymorphisms to be significantly associated (P<0·01) with systolic blood pressure although all were in linkage disequilibrium. No significant associations were identified between single nucleotide polymorphisms and renal function or chronic kidney disease. Results of this pilot study suggest that genetic variation in UMOD might influence blood pressure in cats, similar to findings in humans. Validation of these results is required.

Highlights

  • Uromodulin, glycosylphosphatidylinositol-anchored protein that is expressed on the luminal surface of renal tubular cells of the thick ascending limb (TAL) of the loop of Henle (Vyletal et al 2010)

  • This study demonstrates that genetic variants in UMOD are significantly and positively associated with systolic blood pressure (SBP) but not with systemic HT as a specific outcome

  • This finding is comparable to the associations that have been made to date in human medicine (Iwai et al 2006, Padmanabhan et al 2010, Han et al 2012)

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Summary

Introduction

Uromodulin, glycosylphosphatidylinositol-anchored protein that is expressed on the luminal surface of renal tubular cells of the thick ascending limb (TAL) of the loop of Henle (Vyletal et al 2010). From this location, yet to be identified proteases release uromodulin into the urine, where it represents one of the most abundant urinary proteins in all mammalian species, and forms high molecular weight polymers (Vyletal et al 2010). Uromodulin has been proposed to play an important role in the formation and trafficking of apical membrane-targeted cargo vesicles. It has been suggested that uromodulin maintains its gellike properties retarding the passive passage of positively-charged electrolytes otherwise known as

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