title: The involvement of sequence variation and expression of CX3CR1 in the pathogenesis of age-related macular degeneration.
abstract: This study examined the association between the sequence variation/expression of CX3CR1, a chemokine receptor, and age-related macular degeneration (AMD). Peripheral blood from 85 AMD patients and 105 subjects without AMD (controls), as well as ocular tissue from 40 pathological sections with AMD and two normal eye sections, were screened for V249I and T280M, two single nucleotide polymorphisms (SNPs) in CX3CR1. An increased prevalence, with the highest odds ratio of 3.57, of the I249 and M280 carriers was found among the AMD cases as compared with the controls. When comparing CX3CR1 expression in the archived eye sections, CX3CR1 transcripts were not detectable in the maculae of AMD eyes bearing T/M280; however, transcripts were detected in the maculae of normal eyes bearing T/T280 or T/M280 as well as in the AMD maculae bearing T/T280. Furthermore, lower CX3CR1 protein expression was observed in the maculae of AMD eyes bearing T/M280 compared with the controls bearing T/T280. The I249 and M280 alleles result in a lowered number of receptor binding sites and a decreased ligand affinity. Our data suggest that a decrease, caused by sequence variation and/or lower CX3CR1 expression, in CX3CR1-induced cellular activities could contribute to AMD development.
authors.affiliation: Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-1857, USA.
authors.forename: Jingsheng
authors.initials: J
authors.lastname: Tuo
authors.forename: Brena C
authors.initials: BC
authors.lastname: Smith
authors.forename: Christine M
authors.initials: CM
authors.lastname: Bojanowski
authors.forename: Annal D
authors.initials: AD
authors.lastname: Meleth
authors.forename: Igal
authors.initials: I
authors.lastname: Gery
authors.forename: Karl G
authors.initials: KG
authors.lastname: Csaky
authors.forename: Emily Y
authors.initials: EY
authors.lastname: Chew
authors.forename: Chi-Chao
authors.initials: CC
authors.lastname: Chan
mesh_terms: D000368:Aged; D000375:Aging / Q000235:genetics* / Q000378:metabolism; D019943:Amino Acid Substitution; D001782:Blood Donors; D000073883:CX3C Chemokine Receptor 1; D016022:Case-Control Studies; D002633:Chemotaxis; D005136:Eye Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D008268:Macular Degeneration / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008875:Middle Aged; D020125:Mutation, Missense; D016017:Odds Ratio; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000096:biosynthesis; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012307:Risk Factors; D044465:White People / Q000235:genetics
chemical_list: D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D005136:Eye Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D019707:Receptors, Chemokine