title: Next generation sequencing search for uromodulin gene variants related with impaired renal function.
abstract: Uromodulin gene (UMOD) mutations have been linked to rare forms of mendelian dominant medullary cystic kidney disease and familial hyperuricemia. In addition, common single nucleotide polymorphisms in the UMOD promoter have been associated with the risk for impaired renal function and chronic kidney disease. Our main purpose was to identify UMOD variants related with impaired renal function in an elderly population. The UMOD gene was next generation sequenced in a total of 100 healthy individuals with normal or reduced renal function [measured as the rate of estimated glomerular filtration (eGFR)]. The identified missense changes and the common promoter rs12917707 polymorphism were determined in individuals with reduced (n = 88) and normal (n = 442) eGFR values. Allele and genotype frequencies were compared between the groups. We only identified a rare UMOD misense change, p.V458L, and the rare leu allele was significantly more frequent in a cohort of individuals with reduced (eGFR < 60) compared to normal eGFR (P = 0.02). The common rs12917707 polymorphism previously linked to renal function and kidney disease was not associated with impaired filtration rate in our cohort. We found a significant effect of the rare p.V458L variant on the value of estimated glomerular filtration. This finding deserves further validation in larger cohorts.
authors.affiliation: Genética Molecular-Laboratorio Medicina, Hospital Universitario Central de Asturias (HUCA), 33011, Oviedo, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Gómez
authors.forename: Carmen
authors.initials: C
authors.lastname: Díaz-Corte
authors.forename: Salvador
authors.initials: S
authors.lastname: Tranche
authors.forename: Francisco
authors.initials: F
authors.lastname: Alvarez
authors.forename: Sara
authors.initials: S
authors.lastname: Iglesias
authors.forename: Belén
authors.initials: B
authors.lastname: Alonso
authors.forename: Eliecer
authors.initials: E
authors.lastname: Coto
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005919:Glomerular Filtration Rate / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D051437:Renal Insufficiency / Q000235:genetics*; D058949:Uromodulin / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: C548612:UMOD protein, human; D058949:Uromodulin