Genome-Wide Meta-Analysis Unravels Interactions between Magnesium Homeostasis and Metabolic Phenotypes.

TitreGenome-Wide Meta-Analysis Unravels Interactions between Magnesium Homeostasis and Metabolic Phenotypes.
Publication TypeJournal Article
Year of Publication2018
AuthorsCorre, T, Arjona, FJ, Hayward, C, Youhanna, S, de Baaij, JHF, Belge, H, Nägele, N, Debaix, H, Blanchard, MG, Traglia, M, Harris, SE, Ulivi, S, Rueedi, R, Lamparter, D, Macé, A, Sala, C, Lenarduzzi, S, Ponte, B, Pruijm, M, Ackermann, D, Ehret, G, Baptista, D, Polasek, O, Rudan, I, Hurd, TW, Hastie, ND, Vitart, V, Waeber, G, Kutalik, Z, Bergmann, S, Vargas-Poussou, R, Konrad, M, Gasparini, P, Deary, IJ, Starr, JM, Toniolo, D, Vollenweider, P, Hoenderop, JGJ, Bindels, RJM, Bochud, M, Devuyst, O
JournalJournal of the American Society of Nephrology
Volume29
Issue1
Pagination335-348
Date Published01/2018
DOI10.1681/ASN.2017030267
ISSN1533-3450
Mots-clésGene-Environment Interaction, Genetic determinants, Magnesium homeostasis, Metabolic syndrome, Tubular transport, Zebrafish
Abstract

Magnesium (Mg2+) homeostasis is critical for metabolism. However, the genetic determinants of the renal handling of Mg2+, which is crucial for Mg2+ homeostasis, and the potential influence on metabolic traits in the general population are unknown. We obtained plasma and urine parameters from 9099 individuals from seven cohorts, and conducted a genome-wide meta-analysis of Mg2+ homeostasis. We identified two loci associated with urinary magnesium (uMg), rs3824347 (P=4.4×10-13) near TRPM6, which encodes an epithelial Mg2+ channel, and rs35929 (P=2.1×10-11), a variant of ARL15, which encodes a GTP-binding protein. Together, these loci account for 2.3% of the variation in 24-hour uMg excretion. In human kidney cells, ARL15 regulated TRPM6-mediated currents. In zebrafish, dietary Mg2+ regulated the expression of the highly conserved ARL15 ortholog arl15b, and arl15b knockdown resulted in renal Mg2+ wasting and metabolic disturbances. Finally, ARL15 rs35929 modified the association of uMg with fasting insulin and fat mass in a general population. In conclusion, this combined observational and experimental approach uncovered a gene-environment interaction linking Mg2+ deficiency to insulin resistance and obesity.

Alternate URL

http://www.ncbi.nlm.nih.gov/pubmed/29093028?dopt=Abstract

First publication date (online)

11/2017

WOS ID (UT)

000419070800033

Alternate JournalJ. Am. Soc. Nephrol.
Citation Key / SERVAL ID8430
Peer reviewRefereed
PubMed ID29093028
                         

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