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Title

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

Authors
Corre, Tanguy
Arjona, Francisco J
Hayward, Caroline
Youhanna, Sonia
de Baaij, Jeroen H F
Belge, Hendrica
Nägele, Nadine
Debaix, Huguette
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Published in Journal of the American Society of Nephrology. 2017, p. ASN.2017030267
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.
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PMID: 29093028
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Structures
Research group Groupe Pierre-Yves Martin (néphrologie) (30)
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CORRE, Tanguy et al. Genome-Wide Meta-Analysis Unravels Interactions between Magnesium Homeostasis and Metabolic Phenotypes. In: Journal of the American Society of Nephrology, 2017, p. ASN.2017030267. https://archive-ouverte.unige.ch/unige:100757

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Deposited on : 2017-12-21

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