title: Polymorphisms in the human CC chemokine receptor-3 gene.
abstract: CC chemokine receptor (CCR)-3 is a seven-transmembrane-spanning G-protein-coupled receptor (GPCR) that is involved in the recruitment of inflammatory cells in allergic responses and acts as a co-receptor for entry of HIV into cells. Selected polymorphisms in GPCRs have been shown to have dramatic effects on the manifestation and/or susceptibility to a variety of diseases. In this report, we tested whether the human CCR-3 gene locus is genetically polymorphic. Using single-stranded conformational polymorphism analysis of genomic DNA, the CCR-3 gene is shown to contain four nucleotide polymorphisms with allele frequencies ranging from 0.005 to 0.13. Two polymorphisms encode for an amino acid change. One of these polymorphisms encodes for a non-conservative change 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 encodes for a leucine to proline substitution in the intracellular cytoplasmic 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 disease processes that involve this receptor.
authors.affiliation: Division of Pulmonary Medicine, Allergy and Clinical Immunology, Department of Pediatrics, Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
authors.forename: N
authors.initials: N
authors.lastname: Zimmermann
authors.forename: J A
authors.initials: JA
authors.lastname: Bernstein
authors.forename: M E
authors.initials: ME
authors.lastname: Rothenberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001249:Asthma / Q000235:genetics / Q000276:immunology; D001483:Base Sequence; D044383:Black People / Q000235:genetics; D002648:Child; D017931:DNA Primers; D006678:HIV / Q000502:physiology; D006801:Humans; D007231:Infant, Newborn; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009820:Ohio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D017433:Protein Structure, Secondary; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000737:chemistry* / Q000235:genetics*; D015728:Receptors, HIV / Q000737:chemistry / Q000235:genetics; D044465:White People / Q000235:genetics; D001741:Black or African American
chemical_list: C515350:CCR3 protein, human; D017931:DNA Primers; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D015728:Receptors, HIV