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.
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.
Kovacs
Alexander
A
Department of Cardiology, Karolinska Hospital, S-17176 Stockholm, Sweden.
Green
Fiona
F
Hansson
Lars-Olof
LO
Lundman
Pia
P
Samnegård
Ann
A
Boquist
Susanna
S
Ericsson
Carl-Göran
CG
Watkins
Hugh
H
Hamsten
Anders
A
Tornvall
Per
P
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
D006147:Guanine; D002097:C-Reactive Protein; D000225:Adenine