POLYMORPHISMS IN THE HUMAN CC-CHEMOKINE RECEPTOR-3 GENE

CC chemokine receptor (CCR)-3 is a seven-transmembrane-spanning G-prot ein-coupled receptor (GPCR) that is involved in the recruitment of inf lammatory cells in allergic responses and acts as a co-receptor for en try of HIV into cells. Selected polymorphisms in GPCRs have been shown to have dramatic effects on the manifestation and/or susceptibility t o a variety of diseases. In this report, we tested whether the human C CR-3 gene locus is genetically polymorphic. Using single-stranded conf ormational polymorphism analysis of genomic DNA, the CCR-3 gene is sho wn to contain four nucleotide polymorphisms with allele frequencies ra nging from 0.005 to 0.13. Two polymorphisms encode for an amino acid c hange. One of these polymorphisms encodes for a non-conservative chang e of arginine to glutamine at position 275 of the third extracellular loop. Stratification of the DNA samples into a population with asthma suggested no change in this allele's frequency. Another polymorphism e ncodes for a leucine to proline substitution in the intracellular cyto plasmic tail of CCR-3. The most frequent polymorphism, T51C, occurs in 26% of individuals and encodes for a silent substitution. Thus, CCR-3 contains several genetic variations which may have consequences in di sease processes that involve this (C) 1998 Elsevier Science B.V. All r ights reserved.