Southeast Asian AE1 associated renal tubular acidosis: cation leak is a class effect

Biochem Biophys Res Commun. 2009 May 15;382(4):668-72. doi: 10.1016/j.bbrc.2009.03.062. Epub 2009 Mar 14.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acidosis, Renal Tubular / genetics*
  • Acidosis, Renal Tubular / metabolism*
  • Animals
  • Anion Exchange Protein 1, Erythrocyte / genetics*
  • Anion Exchange Protein 1, Erythrocyte / metabolism*
  • Humans
  • Malaria / genetics*
  • Mutation
  • Xenopus laevis

Substances

  • Anion Exchange Protein 1, Erythrocyte