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: Stephen Walsh, Franck Borgese, Nicole Gabillat, Helene Guizouarn
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 382 Issue 4 Pg. 668-72 (May 15 2009) ISSN: 1090-2104 [Electronic] United States
• PMID: 19289107 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anion Exchange Protein 1, Erythrocyte

Topics

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