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

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. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.