title: A novel common single nucleotide polymorphism in the promoter region of the C-reactive protein gene associated with the plasma concentration of C-reactive protein.
abstract: The plasma CRP concentration has consistently been shown to be associated with the risk of future coronary heart disease (CHD) and recent studies have suggested that CRP has a pathogenic role in CHD. Family studies and genotype-phenotype association studies of known polymorphisms in the intron, second exon and 3'-untranslated region (UTR) have suggested that plasma CRP concentrations are under genetic control. However, no functional polymorphisms have so far been reported in the promoter region of the CRP gene. Screening of 1600 base pair (bp) of the promoter region of the CRP gene, using denaturing high performance liquid chromatography, revealed two novel common single nucleotide polymorphisms (SNPs). One of them, a three allelic SNP located at position -286 from the transcription start, was strongly associated with the plasma CRP concentration, predominantly in patients with CHD. No difference in allele frequency was seen between middle-aged post-infarction patients and population-based controls. The prognostic role and therapeutic implications in CHD and the functionality of this polymorphism remain to be determined.
authors.affiliation: Department of Cardiology, Karolinska Hospital, S-17176 Stockholm, Sweden.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kovacs
authors.forename: Fiona
authors.initials: F
authors.lastname: Green
authors.forename: Lars-Olof
authors.initials: LO
authors.lastname: Hansson
authors.forename: Pia
authors.initials: P
authors.lastname: Lundman
authors.forename: Ann
authors.initials: A
authors.lastname: Samnegård
authors.forename: Susanna
authors.initials: S
authors.lastname: Boquist
authors.forename: Carl-Göran
authors.initials: CG
authors.lastname: Ericsson
authors.forename: Hugh
authors.initials: H
authors.lastname: Watkins
authors.forename: Anders
authors.initials: A
authors.lastname: Hamsten
authors.forename: Per
authors.initials: P
authors.lastname: Tornvall
mesh_terms: D000225:Adenine; D000368:Aged; D002097:C-Reactive Protein / Q000235:genetics* / Q000378:metabolism*; D016022:Case-Control Studies; D003327:Coronary Disease / Q000097:blood* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006147:Guanine; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
chemical_list: D006147:Guanine; D002097:C-Reactive Protein; D000225:Adenine