Associations between connexin37 gene polymorphism and markers of subclinical atherosclerosis: The Cardiovascular Risk in Young Finns study



      Connexin37 (cx37) C1019T polymorphism has been shown to associate with coronary artery disease in different populations. We investigated whether this polymorphism associates with carotid artery intima–media thickness (IMT), carotid artery compliance (CAC) and brachial artery flow mediated dilatation (FMD) – i.e., early ultrasound markers of subclinical atherosclerosis – in a clinically healthy population of young Finnish adults.

      Methods and results

      1440 individuals from the Cardiovascular Risk in Young Finns study were genotyped and studied using cardiovascular risk factor and ultrasound data obtained in 2001. In linear regression models, no significant association between the cx37 polymorphism and carotid IMT, CAC or brachial artery FMD (ANOVA, p = 0.159, 0.151 and 0.547), respectively, was found in the whole population or in women and men separately.


      The connexin37 C1019T polymorphism is not related with markers of subclinical atherosclerosis in young adults.


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


        • Fox C.S.
        • Polak J.F.
        • Chazaro I.
        • et al.
        Genetic and environmental contributions to atherosclerosis phenotypes in men and women: heritability of carotid intima–media thickness in the Framingham Heart Study.
        Stroke. 2003; 34: 397-401
        • Espeland M.A.
        • Tang R.
        • Terry J.G.
        • Davis D.H.
        • Mercuri M.
        • Crouse 3rd., J.R.
        Associations of risk factors with segment-specific intimal–medial thickness of the extracranial carotid artery.
        Stroke. 1999; 30: 1047-1055
        • Folsom A.R.
        • Eckfeldt J.H.
        • Weitzman S.
        • et al.
        Relation of carotid artery wall thickness to diabetes mellitus, fasting glucose and insulin, body size, and physical activity. Atherosclerosis Risk in Communities (ARIC) Study Investigators.
        Stroke. 1994; 25: 66-73
        • Järvisalo M.J.
        • Jartti L.
        • Näntö-Salonen K.
        • et al.
        Increased aortic intima–media thickness: a marker of preclinical atherosclerosis in high-risk children.
        Circulation. 2001; 104: 2943-2947
        • Pauciullo P.
        • Iannuzzi A.
        • Sartorio R.
        • et al.
        Increased intima–media thickness of the common carotid artery in hypercholesterolemic children.
        Arterioscler Thromb. 1994; 14: 1075-1079
        • Davis P.H.
        • Dawson J.D.
        • Riley W.A.
        • Lauer R.M.
        Carotid intimal–medial thickness is related to cardiovascular risk factors measured from childhood through middle age: the Muscatine Study.
        Circulation. 2001; 104: 2815-2819
        • Raitakari O.T.
        • Juonala M.
        • Kähönen 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
        • Li S.
        • Chen W.
        • Srinivasan S.R.
        • et al.
        Childhood cardiovascular risk factors and carotid vascular changes in adulthood: the Bogalusa Heart Study.
        JAMA. 2003; 290: 2271-2276
        • Cuomo S.
        • Guarini P.
        • Gaeta G.
        • et al.
        Increased carotid intima–media thickness in children-adolescents, and young adults with a parental history of premature myocardial infarction.
        Eur Heart J. 2002; 23: 1345-1350
        • Jousilahti P.
        • Puska P.
        • Vartiainen E.
        • Pekkanen J.
        • Tuomilehto J.
        Parental history of premature coronary heart disease: an independent risk factor of myocardial infarction.
        J Clin Epidemiol. 1996; 49: 497-503
        • Blacher J.
        • Pannier B.
        • Guerin A.P.
        • Marchais S.J.
        • Safar M.E.
        • London G.M.
        Carotid arterial stiffness as a predictor of cardiovascular and all-cause mortality in end-stage renal disease.
        Hypertension. 1998; 32: 570-574
        • Juonala M.
        • Järvisalo M.J.
        • Mäki-Torkko N.
        • Kähönen M.
        • Viikari J.S.
        • Raitakari O.T.
        Risk factors identified in childhood and decreased carotid artery elasticity in adulthood: the Cardiovascular Risk in Young Finns Study.
        Circulation. 2005; 112: 1486-1493
        • Ferreira I.
        • Henry R.M.
        • Twisk J.W.
        • van Mechelen W.
        • Kemper H.C.
        • Stehouwer C.D.
        The metabolic syndrome, cardiopulmonary fitness, and subcutaneous trunk fat as independent determinants of arterial stiffness: the Amsterdam Growth and Health Longitudinal Study.
        Arch Intern Med. 2005; 165: 875-882
        • Celermajer D.S.
        • Sorensen K.E.
        • Gooch V.M.
        • et al.
        Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis.
        Lancet. 1992; 340: 1111-1115
        • Neunteufl T.
        • Katzenschlager R.
        • Hassan A.
        • et al.
        Systemic endothelial dysfunction is related to the extent and severity of coronary artery disease.
        Atherosclerosis. 1997; 129: 111-118
        • Sosa-Melgarejo J.A.
        • Berry C.L.
        Myoendothelial contacts in arteriolosclerosis.
        J Pathol. 1992; 167: 235-239
        • Griendling K.K.
        • Alexander R.W.
        Endothelial control of the cardiovascular system: recent advances.
        FASEB J. 1996; 10: 283-292
        • Goodenough D.A.
        • Goliger J.A.
        • Paul D.L.
        Connexins, connexons, and intercellular communication.
        Annu Rev Biochem. 1996; 65: 475-502
        • Bruzzone R.
        • Haefliger J.A.
        • Gimlich R.L.
        • Paul D.L.
        Connexin40, a component of gap junctions in vascular endothelium, is restricted in its ability to interact with other connexins.
        Mol Biol Cell. 1993; 4: 7-20
        • Gabriels J.E.
        • Paul D.L.
        Connexin43 is highly localized to sites of disturbed flow in rat aortic endothelium but connexin37 and connexin40 are more uniformly distributed.
        Circ Res. 1998; 83: 636-643
        • Yeh H.I.
        • Dupont E.
        • Coppen S.
        • Rothery S.
        • Severs N.J.
        Gap junction localization and connexin expression in cytochemically identified endothelial cells of arterial tissue.
        J Histochem Cytochem. 1997; 45: 539-550
        • Cai W.J.
        • Koltai S.
        • Kocsis E.
        • Scholz D.
        • Schaper W.
        • Schaper J.
        Connexin37, not Cx40 and Cx43, is induced in vascular smooth muscle cells during coronary arteriogenesis.
        J Mol Cell Cardiol. 2001; 33: 957-967
        • Yeh H.I.
        • Lai Y.J.
        • Chang H.M.
        • Ko Y.S.
        • Severs N.J.
        • Tsai C.H.
        Multiple connexin expression in regenerating arterial endothelial gap junctions.
        Arterioscler Thromb Vasc Biol. 2000; 20: 1753-1762
        • Yeh H.I.
        • Chang H.M.
        • Lu W.W.
        • et al.
        Age-related alteration of gap junction distribution and connexin expression in rat aortic endothelium.
        J Histochem Cytochem. 2000; 48: 1377-1389
        • Yeh H.I.
        • Lu C.S.
        • Wu Y.J.
        • et al.
        Reduced expression of endothelial connexin37 and connexin40 in hyperlipidemic mice: recovery of connexin37 after 7-day simvastatin treatment.
        Arterioscler Thromb Vasc Biol. 2003; 23: 1391-1397
        • Li H.
        • Brodsky S.
        • Kumari S.
        • et al.
        Paradoxical overexpression and translocation of connexin43 in homocysteine-treated endothelial cells.
        Am J Physiol Heart Circ Physiol. 2002; 282: H2124-H2133
        • van Rijen H.V.
        • van Kempen M.J.
        • Postma S.
        • Jongsma H.J.
        Tumour necrosis factor alpha alters the expression of connexin43, connexin40, and connexin37 in human umbilical vein endothelial cells.
        Cytokine. 1998; 10: 258-264
        • Hu J.
        • Cotgreave I.A.
        Differential regulation of gap junctions by proinflammatory mediators in vitro.
        J Clin Invest. 1997; 99: 2312-2316
        • Kwak B.R.
        • Mulhaupt F.
        • Veillard N.
        • Gros D.B.
        • Mach F.
        Altered pattern of vascular connexin expression in atherosclerotic plaques.
        Arterioscler Thromb Vasc Biol. 2002; 22: 225-230
        • Looft-Wilson R.C.
        • Payne G.W.
        • Segal S.S.
        Connexin expression and conducted vasodilation along arteriolar endothelium in mouse skeletal muscle.
        J Appl Physiol. 2004; 97: 1152-1158
        • Boerma M.
        • Forsberg L.
        • Van Zeijl L.
        • et al.
        A genetic polymorphism in connexin 37 as a prognostic marker for atherosclerotic plaque development.
        J Intern Med. 1999; 246: 211-218
        • Yeh H.I.
        • Chou Y.
        • Liu H.F.
        • Chang S.C.
        • Tsai C.H.
        Connexin37 gene polymorphism and coronary artery disease in Taiwan.
        Int J Cardiol. 2001; 81: 251-255
        • Hirashiki A.
        • Yamada Y.
        • Murase Y.
        • et al.
        Association of gene polymorphisms with coronary artery disease in low- or high-risk subjects defined by conventional risk factors.
        J Am Coll Cardiol. 2003; 42: 1429-1437
        • Yamada Y.
        • Izawa H.
        • Ichihara S.
        • et al.
        Prediction of the risk of myocardial infarction from polymorphisms in candidate genes.
        N Engl J Med. 2002; 347: 1916-1923
        • Listi F.
        • Candore G.
        • Lio D.
        • et al.
        Association between C1019T polymorphism of connexin37 and acute myocardial infarction: a study in patients from sicily.
        Int J Cardiol. 2005; 102: 269-271
        • Åkerblom 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-Kähönen 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
        • Juonala M.
        • Viikari J.S.
        • Laitinen T.
        • et al.
        Interrelations between brachial endothelial function and carotid intima–media thickness in young adults: the cardiovascular risk in young Finns study.
        Circulation. 2004; 110: 2918-2923
        • Livak K.J.
        Allelic discrimination using fluorogenic probes and the 5’ nuclease assay.
        Genet Anal. 1999; 14: 143-149
        • Wong C.W.
        • Christen T.
        • Pfenniger A.
        • James R.W.
        • Kwak B.R.
        Do allelic variants of the connexin37 1019 gene polymorphism differentially predict for coronary artery disease and myocardial infarction?.
        Atherosclerosis. 2007; 191: 355-361