Functional analysis of mutant SLCO2A1 transporters found in patients with chronic enteropathy associated with SLCO2A1.

BACKGROUND AND AIM: Chronic enteropathy associated with the solute carrier organic anion transporter family member 2A1 (SLCO2A1), or CEAS, causes anemia and hypoalbuminemia in young people. Dysfunction of the SLCO2A1 transporter protein is thought to involve genetic mutation, but mutant proteins have not been functionally characterized. We examined the prostaglandin E2 (PGE2 ) transport ability of recombinant SLCO2A1 proteins containing 11 SLCO2A1 mutations found in CEAS patients.

METHODS: Wild-type and mutant SLCO2A1 proteins were forcibly expressed in Xenopus laevis oocytes, and measurements of PGE2 uptake and transport capacity were compared. The membrane protein topology and functionality of the eight SLCO2A1 mutations involving single-nucleotide substitutions were predicted using computer analysis.

RESULTS: The extent of functional disruption of the 11 SLCO2A1 mutations identified in CEAS patients was variable, with 10 mutations (421GT, 547GA, 664GA, 770GA, 830dupT, 830delT, 940 + 1GA, 1372GT, 1647GT, and 1807CT) resulting in loss or reduction of PGE2 transport, excluding 97GC.

CONCLUSION: PGE2 transport ability of recombinant SLCO2A1 in X. laevis oocytes was hindered in 10/11 SLCO2A1 mutations identified in patients with CEAS. Further studies on the relationships between the different mutations and PGE2 transport and clinical features, such as severity, are needed.