PUBLICATION

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

Authors
Corre, T., Arjona, F.J., Hayward, C., Youhanna, S., de Baaij, J.H.F., Belge, H., Nägele, N., Debaix, H., Blanchard, M.G., Traglia, M., Harris, S.E., 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, T.W., Hastie, N.D., Vitart, V., Waeber, G., Kutalik, Z., Bergmann, S., Vargas-Poussou, R., Konrad, M., Gasparini, P., Deary, I.J., Starr, J.M., Toniolo, D., Vollenweider, P., Hoenderop, J.G.J., Bindels, R.J.M., Bochud, M., Devuyst, O.
ID
ZDB-PUB-171103-12
Date
2017
Source
Journal of the American Society of Nephrology : JASN   29(1): 335-348 (Journal)
Registered Authors
Arjona, F.J., Hastie, Nicholas D.
Keywords
Gene-environment interaction, Genetic determinants, Magnesium homeostasis, Metabolic syndrome, Tubular transport, zebrafish
MeSH Terms
  • Zebrafish
  • Kidney/metabolism*
  • Gene-Environment Interaction
  • Homeostasis/genetics*
  • Animals
  • Polymorphism, Single Nucleotide
  • TRPM Cation Channels/genetics*
  • Humans
  • Mice
  • Magnesium/administration & dosage
  • Magnesium/blood*
  • Magnesium/urine*
  • Adiposity/genetics
  • Insulin Resistance/genetics
  • RNA, Messenger/metabolism
  • Genome-Wide Association Study
  • ADP-Ribosylation Factors/genetics*
  • Obesity/genetics
  • Insulin/blood
  • Phenotype
(all 20)
PubMed
29093028 Full text @ J. Am. Soc. Nephrol.
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.
Genes / Markers
Figures
No images available
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Your Input Welcome
We welcome your input and comments. Please use this form to recommend updates to the information in ZFIN. We appreciate as much detail as possible and references as appropriate. We will review your comments promptly.
Citation
Corre, T., Arjona, F.J., Hayward, C., Youhanna, S., de Baaij, J.H.F., Belge, H., Nägele, N., Debaix, H., Blanchard, M.G., Traglia, M., Harris, S.E., 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, T.W., Hastie, N.D., Vitart, V., Waeber, G., Kutalik, Z., Bergmann, S., Vargas-Poussou, R., Konrad, M., Gasparini, P., Deary, I.J., Starr, J.M., Toniolo, D., Vollenweider, P., Hoenderop, J.G.J., Bindels, R.J.M., Bochud, M., Devuyst, O. (2017) Genome-Wide Meta-Analysis Unravels Interactions between Magnesium Homeostasis and Metabolic Phenotypes. Journal of the American Society of Nephrology : JASN. 29(1):335-348.