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Genome-wide Association Study of 24-Hour Urinary Excretion of Calcium, Magnesium, and Uric Acid
OBJECTIVES: The urinary excretion of organic and inorganic substances and their concentrations have attracted extensive attention for their role in the pathogenesis of urinary stone disease. The urinary excretion of specific factors associates with sex and age and seems to have a hereditary componen...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978610/ https://www.ncbi.nlm.nih.gov/pubmed/31993563 http://dx.doi.org/10.1016/j.mayocpiqo.2019.08.007 |
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author | Ware, Erin B. Smith, Jennifer A. Zhao, Wei Ganesvoort, Ron T. Curhan, Gary C. Pollak, Martin Mount, David B. Turner, Stephen T. Chen, Guotao Shah, Ronak Jagdeep Kardia, Sharon L.R. Lieske, John C. |
author_facet | Ware, Erin B. Smith, Jennifer A. Zhao, Wei Ganesvoort, Ron T. Curhan, Gary C. Pollak, Martin Mount, David B. Turner, Stephen T. Chen, Guotao Shah, Ronak Jagdeep Kardia, Sharon L.R. Lieske, John C. |
author_sort | Ware, Erin B. |
collection | PubMed |
description | OBJECTIVES: The urinary excretion of organic and inorganic substances and their concentrations have attracted extensive attention for their role in the pathogenesis of urinary stone disease. The urinary excretion of specific factors associates with sex and age and seems to have a hereditary component, but the precise genomic determinants remain ill-defined. METHODS: Genome-wide association studies previously conducted in 3 cohorts (Genetic Epidemiology Network of Arteriopathy study, January 1, 2006, through December 31, 2012; the combined Nurses’ Health Study (NHS), NHS II, and Health Professionals Follow-up Study, January 1, 1994, through December 31, 2003; and the Prevention of Renal and Vascular End-stage Disease study, January 1, 1997, through December 31, 1998) were combined into meta-analyses to evaluate genetic associations with available urinary phenotypes relevant to stone pathogenesis (calcium, magnesium, and uric acid excretion; total urine volume). RESULTS: One region on chromosome 9q21.13 showed strong evidence of an association with urinary magnesium excretion. The strongest signal in this region was near TRPM6, whose protein product mediates magnesium transport in the colon and kidney, and C9orf40, C9orf41, NMRK1, and OSTF1 (rs1176815; P=1.70×10(–14), with each copy of the A allele corresponding to a daily 5.29-mg decrease in magnesium excretion). The single nucleotide polymorphism (SNP) that achieved genome-wide significance for calcium excretion (rs17216707 on chromosome 20; P=1.12×10(–8)) was previously associated with fibroblast growth factor 23 levels, which regulate phosphorus and vitamin D metabolism. Urine volume and uric acid excretion did not have any genome-wide significant SNPs. CONCLUSION: Common variants near genes important for magnesium metabolism and bone health associate with urinary magnesium and calcium excretion. |
format | Online Article Text |
id | pubmed-6978610 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-69786102020-01-28 Genome-wide Association Study of 24-Hour Urinary Excretion of Calcium, Magnesium, and Uric Acid Ware, Erin B. Smith, Jennifer A. Zhao, Wei Ganesvoort, Ron T. Curhan, Gary C. Pollak, Martin Mount, David B. Turner, Stephen T. Chen, Guotao Shah, Ronak Jagdeep Kardia, Sharon L.R. Lieske, John C. Mayo Clin Proc Innov Qual Outcomes Original Article OBJECTIVES: The urinary excretion of organic and inorganic substances and their concentrations have attracted extensive attention for their role in the pathogenesis of urinary stone disease. The urinary excretion of specific factors associates with sex and age and seems to have a hereditary component, but the precise genomic determinants remain ill-defined. METHODS: Genome-wide association studies previously conducted in 3 cohorts (Genetic Epidemiology Network of Arteriopathy study, January 1, 2006, through December 31, 2012; the combined Nurses’ Health Study (NHS), NHS II, and Health Professionals Follow-up Study, January 1, 1994, through December 31, 2003; and the Prevention of Renal and Vascular End-stage Disease study, January 1, 1997, through December 31, 1998) were combined into meta-analyses to evaluate genetic associations with available urinary phenotypes relevant to stone pathogenesis (calcium, magnesium, and uric acid excretion; total urine volume). RESULTS: One region on chromosome 9q21.13 showed strong evidence of an association with urinary magnesium excretion. The strongest signal in this region was near TRPM6, whose protein product mediates magnesium transport in the colon and kidney, and C9orf40, C9orf41, NMRK1, and OSTF1 (rs1176815; P=1.70×10(–14), with each copy of the A allele corresponding to a daily 5.29-mg decrease in magnesium excretion). The single nucleotide polymorphism (SNP) that achieved genome-wide significance for calcium excretion (rs17216707 on chromosome 20; P=1.12×10(–8)) was previously associated with fibroblast growth factor 23 levels, which regulate phosphorus and vitamin D metabolism. Urine volume and uric acid excretion did not have any genome-wide significant SNPs. CONCLUSION: Common variants near genes important for magnesium metabolism and bone health associate with urinary magnesium and calcium excretion. Elsevier 2019-11-22 /pmc/articles/PMC6978610/ /pubmed/31993563 http://dx.doi.org/10.1016/j.mayocpiqo.2019.08.007 Text en © 2019 THE AUTHORS https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Ware, Erin B. Smith, Jennifer A. Zhao, Wei Ganesvoort, Ron T. Curhan, Gary C. Pollak, Martin Mount, David B. Turner, Stephen T. Chen, Guotao Shah, Ronak Jagdeep Kardia, Sharon L.R. Lieske, John C. Genome-wide Association Study of 24-Hour Urinary Excretion of Calcium, Magnesium, and Uric Acid |
title | Genome-wide Association Study of 24-Hour Urinary Excretion of Calcium, Magnesium, and Uric Acid |
title_full | Genome-wide Association Study of 24-Hour Urinary Excretion of Calcium, Magnesium, and Uric Acid |
title_fullStr | Genome-wide Association Study of 24-Hour Urinary Excretion of Calcium, Magnesium, and Uric Acid |
title_full_unstemmed | Genome-wide Association Study of 24-Hour Urinary Excretion of Calcium, Magnesium, and Uric Acid |
title_short | Genome-wide Association Study of 24-Hour Urinary Excretion of Calcium, Magnesium, and Uric Acid |
title_sort | genome-wide association study of 24-hour urinary excretion of calcium, magnesium, and uric acid |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978610/ https://www.ncbi.nlm.nih.gov/pubmed/31993563 http://dx.doi.org/10.1016/j.mayocpiqo.2019.08.007 |
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