title: Evaluation of the G protein coupled receptor-75 (GPR75) in age related macular degeneration.
abstract: BACKGROUND
  A long term project was initiated to identify and to characterise genes that are expressed exclusively or preferentially in the retina as candidates for a genetic susceptibility to age related macular degeneration (AMD). A transcript represented by a cluster of five human expressed sequence tags (ESTs) derived exclusively from retinal cDNA libraries was identified.
  
  
  METHODS
  Northern blot and RT-PCR analyses confirmed preferential retinal expression of the gene, which encodes a G protein coupled receptor, GPR75. Following isolation of the full length cDNA and determination of the genomic organisation, the coding sequence of GPR75 was screened for mutations in 535 AMD patients and 252 controls from Germany, the United States, and Italy. Employed methods included single stranded conformational polymorphism (SSCP) analysis, denaturing high performance liquid chromatography (DHPLC), and direct sequencing.
  
  
  RESULTS
  Nine different sequence variations were identified in patients and control individuals. Three of these (-30A>C, 150G>A, and 346G>A) likely represent polymorphic variants. Each of six alterations (-4G>A, N78K, P99L, S108T, T135P, and Q234X) were found once in single AMD patients and were considered variants that could affect the protein function and potentially cause retinal pathology.
  
  
  CONCLUSIONS
  The presence of six potential pathogenic variants in a cohort of 535 AMD patients alone does not provide statistically significant evidence for the association of sequence variation in GPR75 with genetic predisposition to AMD. However, a possible connection between the variants and age related retinal pathology cannot be discarded. Functional studies are needed to clarify the role of GPR75 in retinal physiology.
authors.affiliation: Institute of Human Genetics, University of Würzburg, Germany.
authors.forename: C G
authors.initials: CG
authors.lastname: Sauer
authors.forename: K
authors.initials: K
authors.lastname: White
authors.forename: H
authors.initials: H
authors.lastname: Stöhr
authors.forename: T
authors.initials: T
authors.lastname: Grimm
authors.forename: A
authors.initials: A
authors.lastname: Hutchinson
authors.forename: P S
authors.initials: PS
authors.lastname: Bernstein
authors.forename: R A
authors.initials: RA
authors.lastname: Lewis
authors.forename: F
authors.initials: F
authors.lastname: Simonelli
authors.forename: D
authors.initials: D
authors.lastname: Pauleikhoff
authors.forename: R
authors.initials: R
authors.lastname: Allikmets
authors.forename: B H
authors.initials: BH
authors.lastname: Weber
mesh_terms: D000328:Adult; D016010:Binomial Distribution; D015152:Blotting, Northern; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D020224:Expressed Sequence Tags; D015723:Gene Library; D020022:Genetic Predisposition to Disease; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational; D011956:Receptors, Cell Surface / Q000235:genetics*; D012160:Retina / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D011956:Receptors, Cell Surface