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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:978.)
© 2007 American Heart Association, Inc.

Letters to the Editor

Mendelian Randomization Suggests No Causal Association Between C-reactive Protein and Carotid Intima-media Thickness in the Young Finns Study

Mika Kivimäki

Department of Epidemiology and Public Health, University College London, UK

Debbie A. Lawlor

Department of Social Medicine, University of Bristol, UK

Carita Eklund

Department of Microbiology and Immunology, University of Tampere Medical School, Finland

George Davey Smith

Department of Social Medicine, University of Bristol, UK

Mikko Hurme

Department of Microbiology and Immunology, Tampere University Hospital and Medical School, Finland

Terho Lehtimäki

Department of Clinical Chemistry, Tampere University Hospital and University of Tampere, Finland

Jorma S.A. Viikari

Department of Medicine, University of Turku, Finland

Olli T. Raitakari

Department of Clinical Physiology, University of Turku, Finland

An extract of the first 250 words of the full text is provided, because this article has no abstract.

To the Editor:

It is unclear whether C-reactive protein (CRP), a nonspecific marker of acute phase inflammatory response, is causally related to arterial intima-media thickness (IMT), a risk factor for coronary heart disease (CHD). Previous evidence from conventional observational studies is inconsistent and suggests that the association may be biased or confounded.¹ According to the Mendelian randomization approach, the genetic variants in the CRP gene (CRP) may represent good instruments for CRP levels that are largely free from reverse causation bias and confounding.¹ If the association between CRP and IMT is causal, then genetic variants in CRP should be related to IMT to the extent predicted by the magnitude of their association with average CRP levels.

We examined the causality between CRP and carotid IMT by determining haplotypes from genetic variants in CRP among 1609 individuals (768 men and 841 women) participating in the Cardiovascular Risk in Young Finns study.² We genotyped 5 single nucleotide polymorphisms (SNPs) in the CRP gene: CRP-717A>G (rs 2794521); CRP-286C>T>A (rs3091244); CRP +1059G>C (rs1800947); CRP +1444T>C (rs1130864); and CRP +1846G>A (rs1205). The SNPs were in Hardy-Weinberg equilibrium and strongly linked D' values ranging between 0.98 to 0.99. After exclusion of rare haplotypes (frequency <1%), 5 haplotypes remained for analysis. We assessed serum high-sensitive CRP in 1980 (at age 3 to 18) and 2001 (at age 24 to 39), and carotid IMT in 2001 to 2002. Potential confounding factors measured included adult biological risk factors (body mass index, systolic and diastolic blood pressure, total, . . . [Full Text of this Article]

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