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Common single nucleotide polymorphisms in transient receptor potential melastatin type 6 increase the risk for proton pump inhibitor-induced hypomagnesemia: a case–control study

Hess, Mark W.; de Baaij, Jeroen H.F.; Broekman, Mark M.T.J.; Bisseling, Tanya M.; Haarhuis, Bertram J.T.; Tan, Adriaan C.I.T.L.; te Morsche, René H.M.; Hoenderop, Joost G.J.; Bindels, René J.M.; Drenth, Joost P.H.

Pharmacogenetics and Genomics: March 2017 - Volume 27 - Issue 3 - p 83–88
doi: 10.1097/FPC.0000000000000259

Objective Proton pump inhibitors (PPIs) are effective drugs for the treatment of gastric acid-related disorders. Serious adverse events are rare for PPIs, but recent data suggest that PPIs cause hypomagnesemia. The aim of this study was to estimate the frequency of PPI-induced hypomagnesemia and to define the risk factors for its development.

Materials and methods A total of 133 chronic users of PPIs were enrolled and patients were distinguished on the basis of their serum Mg2+ concentrations. Common single nucleotide polymorphisms (SNPs) in the candidate gene, transient receptor potential melastatin type 6 (TRPM6), were screened.

Results Seventeen out of 133 patients had PPI-induced hypomagnesemia. The duration of PPI use was longer in those with hypomagnesemia (7.7 vs. 5.2 years). Two common SNPs in TRPM6 (rs3750425 and rs2274924) increased the risk for PPI-induced hypomagnesemia by 5.8-fold.

Conclusion We found hypomagnesemia in 13% of PPI users. SNPs in TRPM6 drive the risk of developing hypomagnesemia during chronic PPI use.

Supplemental Digital Content is available in the text.

Departments of aPhysiology

bGastroenterology and Hepatology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen

cDepartment of Gastroenterology, Bernhoven Hospital, Uden

dDepartment of Gastroenterology, Canisius-Wilhelmina-Hospital, Nijmegen, the Netherlands

* Mark W. Hess and Jeroen H.F. de Baaij contributed equally to the writing of this article.

Correspondence to René J.M. Bindels, PhD, Department of Physiology, Radboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, the Netherlands Tel: +31 24 361 34 26; e-mail:

Received June 6, 2016

Accepted November 11, 2016

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