Genetic variants of calcium and vitamin D metabolism in kidney stone disease
Howles SA, Wiberg A, Goldsworthy M, Bayliss AL, Gluck AK, Ng M, Grout E, Tanikawa C, Kamatani Y, Terao C, Takahashi A, Kubo M, Matsuda K, Thakker RV, Turney BW, Furniss D
Nature communications · 118 citas
Cómo se estudió
- Diseño
- Metaanálisis (indexado por PubMed)
- Estudiado en
- Personas, más trabajo en animales o laboratorio
- Resultado principal
- Eventos clínicos como enfermedad o muerte
Quién lo pagó
- Financiación
- Financiación independiente
- Organización sin fines de lucro
- Wellcome Trust
- Gobierno
- National Institute for Health and Care Research
- Organización sin fines de lucro
- Kidney Research UK
- Gobierno
- Medical Research Council
- Gobierno
- Japan Society for the Promotion of Science
- Gobierno
- NIHR Oxford Biomedical Research Centre
- Universidad u hospital
- Oxford Biomedical Research Centre
- Gobierno
- National Institute for Health Research (NIHR)
- Subvenciones
- Japan Society for the Promotion of Science (19H03881); Wellcome Trust (204826/Z/16/Z); National Institute for Health and Care Research (CL-2015-13-005); Wellcome Trust (106995); Medical Research Council (MR/N001524/1); Japan Society for the Promotion of Science (19K22525); Wellcome Trust (NF-SI-0514-10091); National Institute for Health and Care Research (NF-SI-0514-10091); Wellcome Trust (106995/Z/15/Z); NIHR Oxford Biomedical Research Centre (NF-SI-0514-10091); Wellcome Trust (10091); Wellcome Trust (204826); Kidney Research UK (RP_030_20180306))
Según 8 financiadores declarados y la declaración de financiación del texto completo.
Publicación
- Publicado
- 2019-11-15 · Nat Commun · vol. 10 · número 1 · pág. 5175
- Editorial
- Nature Portfolio
- Citado
- 145 citas · más que el 98% de estudios similares · 8.1× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 70 trabajos
- Acceso
- Acceso abierto (revista) · CC-BY
- Áreas de investigación
- Kidney Stones and Urolithiasis Treatments · Parathyroid Disorders and Treatments · Genetic Associations and Epidemiology
- Palabras clave
- kidney stones, calcium metabolism, vitamin D metabolism, CYP24A1, WDR72, BCR, genetic loci, serum calcium, urinary calcium excretion, cinacalcet, vitamin D supplementation, recurrent kidney stones
- MeSH
- humans, kidney calculi, calcium, diacylglycerol kinase, vitamin d, proteins, receptors, calcium-sensing, prospective studies, genotype, polymorphism, single nucleotide, adult, aged, middle aged, japan, female, male, genetic variation, genome-wide association study, united kingdom, asian people, white people
16 autores
- Sarah Howles🇬🇧 · autor de correspondenciaUniversity of Oxford
- Akira Wiberg🇬🇧University of Oxford
- Michelle E. Goldsworthy🇬🇧University of Oxford
- Asha L. Bayliss🇬🇧University of Oxford
- Anna Gluck🇬🇧University of Oxford
- Michael Ng🇬🇧University of Oxford
- Emily Grout🇬🇧University of Oxford
- Chizu Tanikawa🇯🇵The University of Tokyo
- Yoichiro Kamatani🇯🇵RIKEN Center for Integrative Medical Sciences
- Chikashi C. Terao🇯🇵RIKEN Center for Integrative Medical Sciences
- Atsushi Takahashi🇯🇵RIKEN Center for Integrative Medical Sciences
- Michiaki Kubo🇯🇵RIKEN Center for Integrative Medical Sciences
- Koichi Matsuda🇯🇵The University of Tokyo
- Rajesh V. Thakker🇬🇧University of Oxford
- Benjamin W. Turney🇬🇧University of Oxford
- Dominic Furniss🇬🇧University of Oxford
Resumen
El texto original del estudio, en el idioma en que se publicó.
Kidney stone disease (nephrolithiasis) is a major clinical and economic health burden with a heritability of ~45-60%. We present genome-wide association studies in British and Japanese populations and a trans-ethnic meta-analysis that include 12,123 cases and 417,378 controls, and identify 20 nephrolithiasis-associated loci, seven of which are previously unreported. A CYP24A1 locus is predicted to affect vitamin D metabolism and five loci, DGKD, DGKH, WDR72, GPIC1, and BCR, are predicted to influence calcium-sensing receptor (CaSR) signaling. In a validation cohort of only nephrolithiasis patients, the CYP24A1-associated locus correlates with serum calcium concentration and a number of nephrolithiasis episodes while the DGKD-associated locus correlates with urinary calcium excretion. In vitro, DGKD knockdown impairs CaSR-signal transduction, an effect rectified with the calcimimetic cinacalcet. Our findings indicate that studies of genotype-guided precision-medicine approaches, including withholding vitamin D supplementation and targeting vitamin D activation or CaSR-signaling pathways in patients with recurrent kidney stones, are warranted.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial (CC BY).
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