Southeast Asian AE1 associated renal tubular acidosis: Cation leak is a class effect
pmid: 19289107
Southeast Asian AE1 associated renal tubular acidosis: Cation leak is a class effect
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.
- Centre Hospitalier Universitaire de Nice France
- French National Centre for Scientific Research France
- University College London United Kingdom
- Nice Sophia Antipolis University France
Xenopus laevis, Anion Exchange Protein 1, Erythrocyte, Mutation, Animals, Humans, Acidosis, Renal Tubular, Malaria
Xenopus laevis, Anion Exchange Protein 1, Erythrocyte, Mutation, Animals, Humans, Acidosis, Renal Tubular, Malaria
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