Cardiology Medical News about risk of coronary heart disease;genetic loci; C-Reactive Protein levels

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Genetic loci associated with C-reactive protein levels and risk of coronary heart disease
JAMA, 07/02/09

Elliott P et al. – Lack of concordance between the effect on coronary heart disease risk of C-reactive protein (CRP) genotypes and CRP levels argues against a causal association of CRP with coronary heart disease.

Methods

Study of the association of genetic loci with CRP levels and risk of coronary heart disease
Genome-wide association (n = 17,967) and replication study (n = 13,615) to identify genetic loci associated with plasma CRP concentrations
Data collection between 1989-2008 and genotyping between 2003-2008
Mendelian randomization study of most closely associated single-nucleotide polymorphism (SNP) in CRP locus and published data on other CRP variants (total 28,112 cases; 100,823 controls)
Investigation of association of CRP variants with coronary heart disease
Comparison of finding with that predicted from meta-analysis of observational studies of CRP levels and risk of coronary heart disease
For other loci associated with CRP levels, selection of most closely associated SNP for testing against coronary heart disease among 14,365 cases and 32,069 control
Main outcome measure: risk of coronary heart disease

Results

Polymorphisms in 5 genetic loci strongly associated with CRP levels (% difference per minor allele): SNP rs6700896 in LEPR, rs4537545 in IL6R, rs7553007 in CRP locus, rs1183910 in HNF1A, and rs4420638 in APOE-CI-CII
Association of SNP rs7553007 in CRP locus with coronary heart disease: odds ratio (OR) of 0.98 per 20% lower CRP level
Mendelian randomization study of variants in CRP locus showed no association with coronary heart disease
SNPs rs6700896 in LEPR, rs4537545 in IL6R, and rs4420638 in APOE-CI-CII cluster all associated with risk of coronary heart disease

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