title: The Fcγ receptor IIA R131H gene polymorphism is associated with endothelial function in patients with hypercholesterolaemia.
abstract: OBJECTIVE
  A gene polymorphism substituting arginine (R) for histidine (H) at position 131 has been described within the Fcγ receptor IIa (FcγRIIa). The R allele is associated with increased binding of CRP and enhanced activation of monocytes. FcγRIIa is also expressed on endothelial cells, and we hypothesized this polymorphism would be associated with alterations of endothelial function.
  
  
  METHODS
  Genomic DNA was extracted and allele-specific PCR reactions were used to determine the FcγRIIa H131R polymorphism in 78 hypercholesterolaemic subjects. Using strain gauge plethysmography, forearm blood flow (FBF) responses were determined to intra-arterial infusion of acetylcholine (ACH), for endothelium-dependent vasodilatation (EDV), to nitroprusside (NP), for endothelium-independent vasodilatation (EIV), to NG-monomethyl-l-arginine (l-NMMA), for basal NO activity, and to ACH in the presence of l-NMMA, to assess the contribution of NO release to EDV.
  
  
  RESULTS
  Homozygous carriers of the H allele (n=30) had significantly better EDV than homozygous carriers of the R allele (n=15), while heterozygotes showed an intermediate phenotype (n=33) (e.g. % increase of FBF to ACH 48μg/min: 527±359% in H/H versus 452±262% in H/R versus 332±413% in R/R, p=0.0012 by 2-way ANOVA). EIV and basal NO activity were not affected by genotype, and co-infusion of l-NMMA abolished the differences in EDV.
  
  
  CONCLUSIONS
  The R allele of the FcγRIIa polymorphism is associated with impaired EDV and reduced NO activity during endothelial cell stimulation. These data suggest that the functional effects of the FcγRIIa H131R gene polymorphism previously observed in vitro translate into clinically relevant alterations of endothelial function in vivo.
authors.affiliation: Department of Nephrology and Hypertension, University of Erlangen-Nuremberg, Germany. Markus.Schneider@glasgow.ac.uk
authors.forename: Markus P
authors.initials: MP
authors.lastname: Schneider
authors.forename: Jeanette H W
authors.initials: JH
authors.lastname: Leusen
authors.forename: Martin
authors.initials: M
authors.lastname: Herrmann
authors.forename: Christoph D
authors.initials: CD
authors.lastname: Garlichs
authors.forename: Kerstin
authors.initials: K
authors.lastname: Amann
authors.forename: Stefan
authors.initials: S
authors.lastname: John
authors.forename: Roland E
authors.initials: RE
authors.lastname: Schmieder
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D002097:C-Reactive Protein / Q000378:metabolism; D004730:Endothelium, Vascular / Q000473:pathology*; D005260:Female; D006720:Homozygote; D006801:Humans; D006937:Hypercholesterolemia / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology; D009569:Nitric Oxide / Q000737:chemistry; D009599:Nitroprusside / Q000494:pharmacology; D010991:Plethysmography / Q000379:methods; D011110:Polymorphism, Genetic; D017452:Receptors, IgG / Q000235:genetics*; D012039:Regional Blood Flow; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: C080568:Fc gamma receptor IIA; D017452:Receptors, IgG; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D002097:C-Reactive Protein