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Contribution title Genome-wide Meta-analysis Unravels Novel Interactions between Magnesium Homeostasis and Metabolic Phenotypes
  1. Tanguy Corre Lausanne University Hospital (CHUV) Presenter
  2. Francisco Arjona Radboud university medical center
  3. René Bindels Radboud university medical center
  4. Olivier Devuyst University of Zürich
  5. Murielle Bochud CHUV
Form of presentation Poster
  • Public health
Abstract Magnesium (Mg2+) homeostasis is critical for metabolism. The genetic determinants of the renal handling of Mg2+, which is crucial for Mg2+ homeostasis, and their potential influence on metabolic traits in the general population are unknown.
Plasma and urine parameters were obtained of 9,099 individuals from seven cohorts for the first genome-wide meta-analysis of Mg2+ homeostasis. Two novel loci, TRPM6 (rs3824347, P=4.4×10-13) and ARL15 (rs35929, P=2.1×10-11), for urinary Mg2+ (uMg) were identified, accounting together for 2.3% of the variation in 24-h uMg excretion.
In human kidney cells, ARL15 was shown to regulate TRPM6-mediated currents. In zebrafish, the expression of the highly conserved ARL15 orthologue, arl15b, was regulated by dietary Mg2+ and arl15b-knockdown resulted in renal Mg2+ wasting and metabolic disturbances. The association of uMg with fasting insulin and fat mass was modified by ARL15 rs35929 in a general population. These studies uncover a novel gene-environment interaction linking Mg2+ deficiency to insulin resistance and obesity.