Exome Analysis Points APOE4 Haplotype as Major Risk to Develop Mesoamerican Nephropathy

The present study aims to characterize the genetic predisposition for the development of Mesoamerican Nephropathy (MeN) in patients from Panama. A Whole Exome Sequencing approach was performed in patients diagnosed with MeN using the criteria of the Pan American Health Organisation (PAHO), and clinical variables were analysed in all patients and in a group of exposed healthy donors and a group of non-exposed healthy donors. We found a variant located in the APOE gene (rs429358 c.388T>C p.(Cys130Arg), identified in 26% (16/61) of patients with MeN, that corresponds to the APOE4 haplotype. In the group of patients with the APOE4 haplotype we have identified that uric acid is elevated when compared to the group of patients without the haplotype. To the best of our knowledge, this is the first study to find variants in the APOE gene as an important genetic risk factor in patients with MeN. These patients have higher hyperuricemia than patients without the variant, which would indicate an important role of uric acid in the pathophysiology of the disease, suggesting the potential use of uric acid-lowering drugs in these patients.