title: Southeast Asian AE1 associated renal tubular acidosis: cation leak is a class effect.
abstract: Anion Exchanger 1 (AE1) is present in the erythrocyte and also in the alpha-intercalated cell; different mutations can cause either red cell disease or distal renal tubular acidosis (dRTA). Recently, we described a cation leak property in four dRTA-causing AE1 mutants, three autosomal dominant (AD) European mutants, one autosomal recessive (AR) from Southeast Asia, G701D. G701D had a very large leak property and is unusually common in SE Asia. We hypothesized that this property might confer a survival advantage. We characterized three other AR dRTA-associated AE1 mutants found in SE Asia, S773P, Delta850 and A858D via transport experiments in AE1-expressing Xenopus oocytes. These three SE Asian mutants also had cation leaks of similar magnitude to that seen in G701D, a property that distinguishes them as a discrete group. The clustering of these cation-leaky AE1 mutations to malarious areas of SE Asia suggests that they may confer malaria resistance.
authors.affiliation: Laboratoire de Biologie et Physiopathologie des Systèmes Intégrés, FRE3094, CNRS-Université de Nice, Bâtiment de Sciences Naturelles, Nice Cedex 2, France. stephen.walsh@ucl.ac.uk
authors.forename: Stephen
authors.initials: S
authors.lastname: Walsh
authors.forename: Franck
authors.initials: F
authors.lastname: Borgese
authors.forename: Nicole
authors.initials: N
authors.lastname: Gabillat
authors.forename: Helene
authors.initials: H
authors.lastname: Guizouarn
mesh_terms: D000141:Acidosis, Renal Tubular / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D001457:Anion Exchange Protein 1, Erythrocyte / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008288:Malaria / Q000235:genetics*; D009154:Mutation; D014982:Xenopus laevis
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte