L'any 1995 l'estudi REGICOR va començar una nova línia d'investigació en genètica. L'objectiu principal era estudiar les variants genètiques que s'associaven amb una susceptibilitat individual més gran per presentar una malaltia cardiovascular. A més a més, es va analitzar la interacció entre els factors genètics i els ambientals, fent una èmfasi especial en la recerca de factors protectors de la malaltia cardiovascular.

En aquest sentit, s'ha dissenyat un estudi de casos i de controls en què participen més de 2.000 casos d'IAM reclutats de manera prospectiva a l'Hospital Universitari de Girona Dr. Josep Trueta i, com a controls sans, els participants en els estudis transversals realitzats els anys 1995, 2000 i 2005. A més, també vàrem fem servir un grup de control de subjectes completament sans de més de 74 anys per identificar factors que predisposin a la longevitat sense malaltia cardiovascular, de manera que es va evitar l'inconvenient dels estudis de casos i controls aparellats per edat, on els controls, aparentment sans, poden acabar desenvolupant la malaltia en el futur.

El nostre interès es va centrar durant els primers anys en l’estudi de gens candidats com PON1, ESR1. En una etapa successiva, i gràcies a la col.laboració en consorcis internacionals, es van realitzar estudis d’associació global del genoma (GWAS de les sigles en anglès Genome Wide Association Study) que han donat fruit a publicacions en revistes d’alt impacte. Altres estudis que s’han estat realitzant en aquesta línia d’investigació inclouen l’avaluació de la millora de la capacitat predictiva de les funcions de risc quan s’afegeix la informació genètica. Finalment, també es pretén avaluar l’impacte de variants epigenètiques (modificacions en l’ADN que no impliquen canvis de seqüència del mateix: fonamentalment metilació del ADN) en el risc de patir malalties cardiovasculars, i com els estils de vida influeixen en la variabilitat epigenètica.

Actualment, els objectius principals d’aquesta línia d’investigació són la identificació de variants genètiques associades a trets cardiovasculars (infart de miocardi, hipertensió i altres factors de risc cardiovascular), la determinació de la capacitat d’aquestes variants per incrementar la capacitat de predicció de les funcions de risc cardiovascular tradicionals, i finalment la avaluació de l’impacte de les variants epigenètiques en trets cardiovasculars.

Sayols-Baixeras S, Subirana I, Fernández-Sanlés A, Sentí M, Lluís-Ganella C, Marrugat J, Elosua R

DNA methylation and obesity traits: An epigenome-wide association study. The REGICOR study.

Epigenetics 2017 12 (10): 909-916, PMID: 29099282

Abstract

Falcone GJ, Biffi A, Devan WJ, Jagiella JM, Schmidt H, Kissela B, Hansen BM, Jimenez-Conde J, Giralt-Steinhauer E, Elosua R, Cuadrado-Godia E, Soriano C, Ayres AM, Schwab K, Pera J, Urbanik A, Rost NS, Goldstein JN, Viswanathan A, Pichler A, Enzinger C, Norrving B, Tirschwell DL, Selim M, Brown DL, Silliman SL, Worrall BB, Meschia JF, Kidwell CS, Montaner J, Fernandez-Cadenas I, Delgado P, Broderick JP, Greenberg SM, Roquer J, Lindgren A, Slowik A, Schmidt R, Flaherty ML, Kleindorfer DO, Langefeld CD, Woo D, Rosand J

Burden of risk alleles for hypertension increases risk of intracerebral hemorrhage.

Stroke 2012 Nov; 43 (11): 2877-83, PMID: 22933587

Abstract

Chambers JC, Zhang W, Sehmi J, Li X, Wass MN, van der Harst P, Hólm H, Sanna S, Kavousi M, Baumeister SE, Coin LJ, Deng G, Gieger C, Heard-Costa NL, Hottenga JJ, Kühnel B, Kumar V, Lagou V, Liang L, Luan J, Vidal PM, Mateo Leach I, O'Reilly PF, Peden JF, Rahmioglu N, Soininen P, Speliotes EK, Yuan X, Thorleifsson G, Alizadeh BZ, Atwood LD, Borecki IB, Brown MJ, Charoen P, Cucca F, Das D, de Geus EJ, Dixon AL, Döring A, Ehret G, Eyjolfsson GI, Farrall M, Forouhi NG, Friedrich N, Goessling W, Gudbjartsson DF, Harris TB, Hartikainen AL, Heath S, Hirschfield GM, Hofman A, Homuth G, Hyppönen E, Janssen HL, Johnson T, Kangas AJ, Kema IP, Kühn JP, Lai S, Lathrop M, Lerch MM, Li Y, Liang TJ, Lin JP, Loos RJ, Martin NG, Moffatt MF, Montgomery GW, Munroe PB, Musunuru K, Nakamura Y, O'Donnell CJ, Olafsson I, Penninx BW, Pouta A, Prins BP, Prokopenko I, Puls R, Ruokonen A, Savolainen MJ, Schlessinger D, Schouten JN, Seedorf U, Sen-Chowdhry S, Siminovitch KA, Smit JH, Spector TD, Tan W, Teslovich TM, Tukiainen T, Uitterlinden AG, van der Klauw MM, Vasan RS, Wallace C, Wallaschofski H, Wichmann HE, Willemsen G, Würtz P, Xu C, Yerges-Armstrong LM, Abecasis GR, Ahmadi KR, Boomsma DI, Caulfield M, Cookson WO, van Duijn CM, Froguel P, Matsuda K, McCarthy MI, Meisinger C, Mooser V, Pietiläinen KH, Schumann G, Snieder H, Sternberg MJ, Stolk RP, Thomas HC, Thorsteinsdottir U, Uda M, Waeber G, Wareham NJ, Waterworth DM, Watkins H, Whitfield JB, Witteman JC, Wolffenbuttel BH, Fox CS, Ala-Korpela M, Stefansson K, Vollenweider P, Völzke H, Schadt EE, Scott J, Jarvelin MR, Elliott P, Kooner JS

Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma.

Nat. Genet. 2011 Nov; 43 (11): 1131-8, PMID: 22001757

Abstract

Lango Allen H, Estrada K, Lettre G, Berndt SI, Weedon MN, Rivadeneira F, Willer CJ, Jackson AU, Vedantam S, Raychaudhuri S, Ferreira T, Wood AR, Weyant RJ, Segrè AV, Speliotes EK, Wheeler E, Soranzo N, Park JH, Yang J, Gudbjartsson D, Heard-Costa NL, Randall JC, Qi L, Vernon Smith A, Mägi R, Pastinen T, Liang L, Heid IM, Luan J, Thorleifsson G, Winkler TW, Goddard ME, Sin Lo K, Palmer C, Workalemahu T, Aulchenko YS, Johansson A, Zillikens MC, Feitosa MF, Esko T, Johnson T, Ketkar S, Kraft P, Mangino M, Prokopenko I, Absher D, Albrecht E, Ernst F, Glazer NL, Hayward C, Hottenga JJ, Jacobs KB, Knowles JW, Kutalik Z, Monda KL, Polašek O, Preuss M, Rayner NW, Robertson NR, Steinthorsdottir V, Tyrer JP, Voight BF, Wiklund F, Xu J, Zhao JH, Nyholt DR, Pellikka N, Perola M, Perry JR, Surakka I, Tammesoo ML, Altmaier EL, Amin N, Aspelund T, Bhangale T, Boucher G, Chasman DI, Chen C, Coin L, Cooper MN, Dixon AL, Gibson Q, Grundberg E, Hao K, Juhani Junttila M, Kaplan LM, Kettunen J, König IR, Kwan T, Lawrence RW, Levinson DF, Lorentzon M, McKnight B, Morris AP, Müller M, Suh Ngwa J, Purcell S, Rafelt S, Salem RM, Salvi E, Sanna S, Shi J, Sovio U, Thompson JR, Turchin MC, Vandenput L, Verlaan DJ, Vitart V, White CC, Ziegler A, Almgren P, Balmforth AJ, Campbell H, Citterio L, De Grandi A, Dominiczak A, Duan J, Elliott P, Elosua R, Eriksson JG, Freimer NB, Geus EJ, Glorioso N, Haiqing S, Hartikainen AL, Havulinna AS, Hicks AA, Hui J, Igl W, Illig T, Jula A, Kajantie E, Kilpeläinen TO, Koiranen M, Kolcic I, Koskinen S, Kovacs P, Laitinen J, Liu J, Lokki ML, Marusic A, Maschio A, Meitinger T, Mulas A, Pare G, Parker AN, Peden JF, Petersmann A, Pichler I, Pietiläinen KH, Pouta A, Ridderstråle M, Rotter JI, Sambrook JG, Sanders AR, Schmidt CO, Sinisalo J, Smit JH, Stringham HM, Bragi Walters G, Widen E, Wild SH, Willemsen G, Zagato L, Zgaga L, Zitting P, Alavere H, Farrall M, McArdle WL, Nelis M, Peters MJ, Ripatti S, van Meurs JB, Aben KK, Ardlie KG, Beckmann JS, Beilby JP, Bergman RN, Bergmann S, Collins FS, Cusi D, den Heijer M, Eiriksdottir G, Gejman PV, Hall AS, Hamsten A, Huikuri HV, Iribarren C, Kähönen M, Kaprio J, Kathiresan S, Kiemeney L, Kocher T, Launer LJ, Lehtimäki T, Melander O, Mosley TH, Musk AW, Nieminen MS, O'Donnell CJ, Ohlsson C, Oostra B, Palmer LJ, Raitakari O, Ridker PM, Rioux JD, Rissanen A, Rivolta C, Schunkert H, Shuldiner AR, Siscovick DS, Stumvoll M, Tönjes A, Tuomilehto J, van Ommen GJ, Viikari J, Heath AC, Martin NG, Montgomery GW, Province MA, Kayser M, Arnold AM, Atwood LD, Boerwinkle E, Chanock SJ, Deloukas P, Gieger C, Grönberg H, Hall P, Hattersley AT, Hengstenberg C, Hoffman W, Lathrop GM, Salomaa V, Schreiber S, Uda M, Waterworth D, Wright AF, Assimes TL, Barroso I, Hofman A, Mohlke KL, Boomsma DI, Caulfield MJ, Cupples LA, Erdmann J, Fox CS, Gudnason V, Gyllensten U, Harris TB, Hayes RB, Jarvelin MR, Mooser V, Munroe PB, Ouwehand WH, Penninx BW, Pramstaller PP, Quertermous T, Rudan I, Samani NJ, Spector TD, Völzke H, Watkins H, Wilson JF, Groop LC, Haritunians T, Hu FB, Kaplan RC, Metspalu A, North KE, Schlessinger D, Wareham NJ, Hunter DJ, O'Connell JR, Strachan DP, Wichmann HE, Borecki IB, van Duijn CM, Schadt EE, Thorsteinsdottir U, Peltonen L, Uitterlinden AG, Visscher PM, Chatterjee N, Loos RJ, Boehnke M, McCarthy MI, Ingelsson E, Lindgren CM, Abecasis GR, Stefansson K, Frayling TM, Hirschhorn JN

Hundreds of variants clustered in genomic loci and biological pathways affect human height.

Nature 2010 Oct; 467 (7317): 832-8, PMID: 20881960

Abstract

Erdmann J, Grosshennig A, Braund PS, König IR, Hengstenberg C, Hall AS, Linsel-Nitschke P, Kathiresan S, Wright B, Trégouët DA, Cambien F, Bruse P, Aherrahrou Z, Wagner AK, Stark K, Schwartz SM, Salomaa V, Elosua R, Melander O, Voight BF, O'Donnell CJ, Peltonen L, Siscovick DS, Altshuler D, Merlini PA, Peyvandi F, Bernardinelli L, Ardissino D, Schillert A, Blankenberg S, Zeller T, Wild P, Schwarz DF, Tiret L, Perret C, Schreiber S, El Mokhtari NE, Schäfer A, März W, Renner W, Bugert P, Klüter H, Schrezenmeir J, Rubin D, Ball SG, Balmforth AJ, Wichmann HE, Meitinger T, Fischer M, Meisinger C, Baumert J, Peters A, Ouwehand WH, Deloukas P, Thompson JR, Ziegler A, Samani NJ, Schunkert H

New susceptibility locus for coronary artery disease on chromosome 3q22.3.

Nat. Genet. 2009 Mar; 41 (3): 280-2, PMID: 19198612

Abstract

Tomás M, Vázquez E, Fernández-Fernández JM, Subirana I, Plata C, Heras M, Vila J, Marrugat J, Valverde MA, Sentí M

Genetic variation in the KCNMA1 potassium channel alpha subunit as risk factor for severe essential hypertension and myocardial infarction.

J. Hypertens. 2008 Nov; 26 (11): 2147-53, PMID: 18854754

Abstract

Domingues-Montanari S, Subirana I, Tomás M, Marrugat J, Sentí M

Association between ESR2 genetic variants and risk of myocardial infarction.

Clin. Chem. 2008 Jul; 54 (7): 1183-9, PMID: 18487282

Abstract

Elosua R, Cupples LA, Fox CS, Polak JF, D'Agostino RA, Wolf PA, O'Donnell CJ, Ordovás JM

Association between well-characterized lipoprotein-related genetic variants and carotid intimal medial thickness and stenosis: The Framingham Heart Study.

Atherosclerosis 2006 Nov; 189 (1): 222-8, PMID: 16430904

Abstract

Manresa JM, Zamora A, Tomás M, Sentí M, Fitó M, Covas MI, Alcántara M, Latorre G, Escurriol V, Domingues S, Marrugat J

Relationship of classical and non-classical risk factors with genetic variants relevant to coronary heart disease.

Eur J Cardiovasc Prev Rehabil 2006 Oct; 13 (5): 738-44, PMID: 17001213

Abstract

Elosua R, Ordovás JM, Cupples LA, Lai CQ, Demissie S, Fox CS, Polak JF, Wolf PA, D'Agostino RB, O'Donnell CJ

Variants at the APOA5 locus, association with carotid atherosclerosis, and modification by obesity: the Framingham Study.

J. Lipid Res. 2006 May; 47 (5): 990-6, PMID: 16474174

Abstract

Sentí M, Fernández-Fernández JM, Tomás M, Vázquez E, Elosua R, Marrugat J, Valverde MA

Protective effect of the KCNMB1 E65K genetic polymorphism against diastolic hypertension in aging women and its relevance to cardiovascular risk.

Circ. Res. 2005 Dec; 97 (12): 1360-5, PMID: 16293791

Abstract

Fernández-Fernández JM, Tomás M, Vázquez E, Orio P, Latorre R, Sentí M, Marrugat J, Valverde MA

Gain-of-function mutation in the KCNMB1 potassium channel subunit is associated with low prevalence of diastolic hypertension.

J. Clin. Invest. 2004 Apr; 113 (7): 1032-9, PMID: 15057310

Abstract

Manresa JM, Tomás M, Ribes E, Pi-Figueras M, Aguilera A, Sentí M, Marrugat J

[Paraoxonase 1 gene 192 polymorphism, physical activity and lipoprotein in women].

Med Clin (Barc) 2004 Feb; 122 (4): 126-9, PMID: 14967092

Abstract

Tomás M, Latorre G, Sentí M, Marrugat J

[The antioxidant function of high density lipoproteins: a new paradigm in atherosclerosis].

Rev Esp Cardiol 2004 Jun; 57 (6): 557-69, PMID: 15225502

Abstract

Elosua R, Ordovás JM, Cupples LA, Fox CS, Polak JF, Wolf PA, D'Agostino RA, O'Donnell CJ

Association of APOE genotype with carotid atherosclerosis in men and women: the Framingham Heart Study.

J. Lipid Res. 2004 Oct; 45 (10): 1868-75, PMID: 15258198

Abstract

Elosua R, Demissie S, Cupples LA, Meigs JB, Wilson PW, Schaefer EJ, Corella D, Ordovás JM

Obesity modulates the association among APOE genotype, insulin, and glucose in men.

Obes. Res. 2003 Dec; 11 (12): 1502-8, PMID: 14694215

Abstract

Sentí M, Tomás M, Fitó M, Weinbrenner T, Covas MI, Sala J, Masiá R, Marrugat J

Antioxidant paraoxonase 1 activity in the metabolic syndrome.

J. Clin. Endocrinol. Metab. 2003 Nov; 88 (11): 5422-6, PMID: 14602783

Abstract

Sentí M, Tomás M, Elosual R, Sala J, Masiá R, Marrugat J

The paraoxonase-1 codon 192 polymorphism is associated with fasting total cholesterol and LDL-cholesterol concentrations only in postmenopausal women. The REGICOR study.

Clin. Chem. Lab. Med. 2002 Jul; 40 (7): 677-83, PMID: 12241013

Abstract

Tomás M, Elosua R, Sentí M, Molina L, Vila J, Anglada R, Fitó M, Covas MI, Marrugat J

Paraoxonase1-192 polymorphism modulates the effects of regular and acute exercise on paraoxonase1 activity.

J. Lipid Res. 2002 May; 43 (5): 713-20, PMID: 11971942

Abstract

Tomás M, Sentí M, Elosua R, Vila J, Sala J, Masiá R, Marrugat J

Interaction between the Gln-Arg 192 variants of the paraoxonase gene and oleic acid intake as a determinant of high-density lipoprotein cholesterol and paraoxonase activity.

Eur. J. Pharmacol. 2001 Dec; 432 (2): 121-8, PMID: 11740946

Abstract

Sentí M, Elosua R, Tomás M, Sala J, Masiá R, Ordovás JM, Shen H, Marrugat J

Physical activity modulates the combined effect of a common variant of the lipoprotein lipase gene and smoking on serum triglyceride levels and high-density lipoprotein cholesterol in men.

Hum. Genet. 2001 Oct; 109 (4): 385-92, PMID: 11702219

Abstract

Sentí M, Tomás M, Vila J, Marrugat J, Elosua R, Sala J, Masiá R

Relationship of age-related myocardial infarction risk and Gln/Arg 192 variants of the human paraoxonase1 gene: the REGICOR study.

Atherosclerosis 2001 Jun; 156 (2): 443-9, PMID: 11395042

Abstract

Sentí M, Tomás M, Marrugat J, Elosua R

Paraoxonase1-192 polymorphism modulates the nonfatal myocardial infarction risk associated with decreased HDLs.

Arterioscler. Thromb. Vasc. Biol. 2001 Mar; 21 (3): 415-20, PMID: 11231922

Abstract

Sentí M, Bosch M, Aubó C, Elosua R, Masiá R, Marrugat J

Relationship of abdominal adiposity and dyslipemic status in women with a common mutation in the lipoprotein lipase gene. The REGICOR investigators.

Atherosclerosis 2000 May; 150 (1): 135-41, PMID: 10781644

Abstract

Sentí M, Aubó C, Elosua R, Sala J, Tomás M, Marrugat J

Effect of physical activity on lipid levels in a population-based sample of men with and without the Arg192 variant of the human paraoxonase gene.

Genet. Epidemiol. 2000 Mar; 18 (3): 276-86, PMID: 10723110

Abstract

Aubó C, Sentí M, Marrugat J, Tomás M, Vila J, Sala J, Masiá R

Risk of myocardial infarction associated with Gln/Arg 192 polymorphism in the human paraoxonase gene and diabetes mellitus. The REGICOR Investigators.

Eur. Heart J. 2000 Jan; 21 (1): 33-8, PMID: 10610741

Abstract

Tomás M, Sentí M, García-Faria F, Vila J, Torrents A, Covas M, Marrugat J

Effect of simvastatin therapy on paraoxonase activity and related lipoproteins in familial hypercholesterolemic patients.

Arterioscler. Thromb. Vasc. Biol. 2000 Sep; 20 (9): 2113-9, PMID: 10978257

Abstract

Sentí M, Aubó C, Bosch M, Pavesi M, Pena A, Masiá R, Marrugat J

Platelet glycoprotein IIb/IIIa genetic polymorphism is associated with plasma fibrinogen levels in myocardial infarction patients. The REGICOR Investigators.

Clin. Biochem. 1998 Nov; 31 (8): 647-51, PMID: 9876897

Abstract