Advertisement

C-reactive protein genetics is associated with carotid artery compliance in men in The Cardiovascular Risk in Young Finns Study

      Abstract

      Although C-reactive protein (CRP) is known to predict cardiovascular events, its status as a causal risk factor is still controversial. CRP gene single nucleotide polymorphisms (SNPs) have been shown to associate with CRP concentration, but no direct independent effect on early atherosclerotic changes has been demonstrated. We aimed to determine if CRP gene polymorphisms or haplotypes are associated with CRP concentration or carotid artery compliance (CAC), an indicator of subclinical atherosclerosis. We genotyped CRP gene polymorphisms −717A > G, −286C > T > A, +1059G > C, +1444C > T and +1846G > A and measured CRP concentration and CAC in 2283 young adults participating in The Cardiovascular Risk in Young Finns Study. A strong association was found between CRP genotypes and CRP concentration, which was also seen at the haplotype level. Linear regression analysis showed an independent effect of each SNP on CRP concentration after adjustment for risk factors, except for +1444 in males. Moreover, −286C > T > A, +1444C > T and +1846G > A were associated with CAC in males, but not in females. Men carrying the SNP −286 allele C had increased CAC after adjusting for risk factors. These data suggest that the presence of high producer CRP genotype is deleterious to carotid elasticity in men.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Steel D.M.
        • Whitehead A.S.
        The major acute phase reactants: C-reactive protein, serum amyloid P component and serum amyloid A protein.
        Immunol Today. 1994; 15: 81-88
        • Yasojima K.
        • Schwab C.
        • McGeer E.G.
        • McGeer P.L.
        Generation of C-reactive protein and complement components in atherosclerotic plaques.
        Am J Pathol. 2001; 158: 1039-1051
        • Ridker P.M.
        • Buring J.E.
        • Shih J.
        • Matias M.
        • Hennekens C.H.
        Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women.
        Circulation. 1998; 98: 731-733
        • Danesh J.
        • Whincup P.
        • Walker M.
        • et al.
        Low grade inflammation and coronary heart disease: prospective study and updated meta-analyses.
        BMJ. 2000; 321: 199-204
        • Danesh J.
        • Wheeler J.G.
        • Hirschfield G.M.
        • et al.
        C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease.
        N Engl J Med. 2004; 350: 1387-1397
        • Jialal I.
        • Devaraj S.
        • Venugopal S.K.
        C-reactive protein: risk marker or mediator in atherothrombosis?.
        Hypertension. 2004; 44: 6-11
        • Sitzer M.
        • Markus H.S.
        • Mendall M.A.
        • et al.
        C-reactive protein and carotid intimal medial thickness in a community population.
        J Cardiovasc Risk. 2002; 9: 97-103
        • Makita S.
        • Nakamura M.
        • Hiramori K.
        The association of C-reactive protein levels with carotid intima-media complex thickness and plaque formation in the general population.
        Stroke. 2005; 36: 2138-2142
        • MacGregor A.J.
        • Gallimore J.R.
        • Spector T.D.
        • Pepys M.B.
        Genetic effects on baseline values of C-reactive protein and serum amyloid a protein: a comparison of monozygotic and dizygotic twins.
        Clin Chem. 2004; 50: 130-134
        • Kushner I.
        • Rzewnicki D.
        • Samols D.
        What does minor elevation of C-reactive protein signify?.
        Am J Med. 2006; 119: e17-e28
        • Miller D.T.
        • Zee R.Y.
        • Suk Danik J.
        • et al.
        Association of common CRP gene variants with CRP levels and cardiovascular events.
        Ann Hum Genet. 2005; 69: 623-638
        • Chen J.
        • Zhao J.
        • Huang J.
        • et al.
        −717A > G polymorphism of human C-reactive protein gene associated with coronary heart disease in ethnic Han Chinese: the Beijing atherosclerosis study.
        J Mol Med. 2005; 83: 72-78
        • Lange L.A.
        • Carlson C.S.
        • Hindorff L.A.
        • et al.
        Association of polymorphisms in the CRP gene with circulating C-reactive protein levels and cardiovascular events.
        JAMA. 2006; 296: 2703-2711
        • Casas J.P.
        • Shah T.
        • Cooper J.
        • et al.
        Insight into the nature of the CRP-coronary event association using Mendelian randomization.
        Int J Epidemiol. 2006; 35: 922-931
        • Raitakari O.T.
        Imaging of subclinical atherosclerosis in children and young adults.
        Ann Med. 1999; 31: 33-40
        • Carlson C.S.
        • Aldred S.F.
        • Lee P.K.
        • et al.
        Polymorphisms within the C-reactive protein (CRP) promoter region are associated with plasma CRP levels.
        Am J Hum Genet. 2005; 77: 64-77
        • Akerblom H.K.
        • Viikari J.
        • Uhari M.
        • et al.
        Atherosclerosis precursors in Finnish children and adolescents. I. General description of the cross-sectional study of 1980, and an account of the children's and families’ state of health.
        Acta Paediatr Scand Suppl. 1985; 318: 49-63
        • Juonala M.
        • Viikari J.S.
        • Hutri-Kahonen N.
        • et al.
        The 21-year follow-up of The Cardiovascular Risk in Young Finns Study: risk factor levels, secular trends and east-west difference.
        J Intern Med. 2004; 255: 457-468
        • Raitakari O.T.
        • Juonala M.
        • Kahonen M.
        • et al.
        Cardiovascular risk factors in childhood and carotid artery intima-media thickness in adulthood: The Cardiovascular Risk in Young Finns Study.
        JAMA. 2003; 290: 2277-2283
        • Juonala M.
        • Jarvisalo M.J.
        • Maki-Torkko N.
        • et al.
        Risk factors identified in childhood and decreased carotid artery elasticity in adulthood: The Cardiovascular Risk in Young Finns Study.
        Circulation. 2005; 112: 1486-1493
        • Raitakari M.
        • Mansikkaniemi K.
        • Marniemi J.
        • Viikari J.S.
        • Raitakari O.T.
        Distribution and determinants of serum high-sensitive C-reactive protein in a population of young adults: The Cardiovascular Risk in Young Finns Study.
        J Intern Med. 2005; 258: 428-434
        • Zee R.Y.
        • Ridker P.M.
        Polymorphism in the human C-reactive protein (CRP) gene, plasma concentrations of CRP, and the risk of future arterial thrombosis.
        Atherosclerosis. 2002; 162: 217-219
        • Davey Smith G.
        • Lawlor D.A.
        • Harbord R.
        • et al.
        Association of C-reactive protein with blood pressure and hypertension: life course confounding and mendelian randomization tests of causality.
        Arterioscler Thromb Vasc Biol. 2005; 25: 1051-1056
        • Reilly M.P.
        • Wolfe M.L.
        • Localio A.R.
        • Rader D.J.
        C-reactive protein and coronary artery calcification: The Study of Inherited Risk of Coronary Atherosclerosis (SIRCA).
        Arterioscler Thromb Vasc Biol. 2003; 23: 1851-1856
      1. Kivimäki M, Lawlor DA, Eklund C, et al. Mendelian randomization suggests no causal association between C-reactive protein and carotid intima-media thickness in the Young Finns Study. Arterioscler Thromb Vasc Biol; 2007 [epub ahead of print].

        • Blacher J.
        • Pannier B.
        • Guerin A.P.
        • et al.
        Carotid arterial stiffness as a predictor of cardiovascular and all-cause mortality in end-stage renal disease.
        Hypertension. 1998; 32: 570-574
        • Katan M.B.
        Apolipoprotein E isoforms, serum cholesterol, and cancer.
        Lancet. 1986; 1: 507-508
        • Kivimaki M.
        • Lawlor D.A.
        • Juonala M.
        • et al.
        Lifecourse socioeconomic position, C-reactive protein, and carotid intima-media thickness in young adults: The Cardiovascular Risk in Young Finns Study.
        Arterioscler Thromb Vasc Biol. 2005; 25: 2197-2202
        • Venugopal S.K.
        • Devaraj S.
        • Jialal I.
        Macrophage conditioned medium induces the expression of C-reactive protein in human aortic endothelial cells: potential for paracrine/autocrine effects.
        Am J Pathol. 2005; 166: 1265-1271
        • Wang H.W.
        • Sui S.F.
        Dissociation and subunit rearrangement of membrane-bound human C-reactive proteins.
        Biochem Biophys Res Commun. 2001; 288: 75-79
        • Diehl E.E.
        • Haines 3rd, G.K.
        • Radosevich J.A.
        • Potempa L.A.
        Immunohistochemical localization of modified C-reactive protein antigen in normal vascular tissue.
        Am J Med Sci. 2000; 319: 79-83
        • Ji S.R.
        • Wu Y.
        • Zhu L.
        • et al.
        Cell membranes and liposomes dissociate C-reactive protein (CRP) to form a new, biologically active structural intermediate: mCRPm.
        FASEB J. 2007; 21: 284-294