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

Genetic variations in the CC chemokine receptor (CCR5) leading to reduced o r absent expression are associated with resistance to human immunodeficienc y 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 previou sly 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 th is position, resulting in protein instability. Moreover, R60S, a mutation i n the first intracellular loop of CCR5 noted in a recent cohort study, like wise results in reduced surface expression and function of CCR5. The presen ce of a homologous, naturally occurring mutation that may be protective aga inst disease thus defines a novel mechanism accounting for the decreased ex pression of these receptors in some individuals.