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Blood, 1 June 2001, Vol. 97, No. 11, pp. 3651-3654

BRIEF REPORT

A homologous naturally occurring mutation in Duffy and CCR5 leading to reduced receptor expression

Daniel Tamasauskas, Vivien Powell, Kalle Saksela, and Karina Yazdanbakhsh

From the Immunochemistry Laboratory, New York Blood Center, New York, NY, and Institute of Medical Technology and Tampere University Hospital, Finland.

Genetic variations in the CC chemokine receptor (CCR5) leading to reduced or absent expression are associated with resistance to human immunodeficiency virus infection and delayed onset of acquired immunodeficiency syndrome. Similarly, lack of the red-cell chemokine receptor Duffy confers protection against malarial infection by Plasmodium vivax. Investigators have previously described a missense mutation (R89C) in the first intracellular loop of Duffy that results in reduced protein expression. The present study shows that the lower Duffy expression is due to loss of the positive charge at this position, resulting in protein instability. Moreover, R60S, a mutation in the first intracellular loop of CCR5 noted in a recent cohort study, likewise results in reduced surface expression and function of CCR5. The presence of a homologous, naturally occurring mutation that may be protective against disease thus defines a novel mechanism accounting for the decreased expression of these receptors in some individuals.

© 2001 by The American Society of Hematology.
 

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