Southeast Asian AE1 associated renal tubular acidosis: Cation leak is a class effect |
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Authors: | Stephen Walsh Franck Borgese Helene Guizouarn |
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Affiliation: | a Laboratoire de Biologie et Physiopathologie des systèmes intégrés, FRE3094, CNRS-Université de Nice, Bâtiment de Sciences Naturelles, 28 Av Valrose, 06102 Nice cedex 2, France b Centre for Nephrology (London Epithelial Group), University College London, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK |
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Abstract: | Anion Exchanger 1 (AE1) is present in the erythrocyte and also in the α-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, Δ850 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. |
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Keywords: | Band 3 Southeast Asia Cation leak dRTA Anion exchanger Malaria |
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