In 1995, the REGICOR study began a new line of genetics research. The primary objective was to study the genetic variations associated with increased individual susceptibility to cardiovascular disease. In addition, the interaction between genetic and environmental factors was studied, with special emphasis on identifying protective factors against cardiovascular disease.
A case-control study was designed that prospectively recruited more than 2,000 participants, including patients with acute myocardial infarction treated at Dr. Josep Trueta University Hospital in Girona and healthy controls from cross-cutting studies conducted in 1995, 2000 and 2005. In addition a control group of completely healthy individuals older than 74 years was recruited to identify factors that predispose for longevity without cardiovascular disease. This avoided the drawback of age-matched case-control studies in which apparently healthy controls may develop the disease in future years.
During the early years, our interest centered around the study of candidate genes such as PON1 and ESR1. Later, and thanks to international consortium collaborations, genome-wide association studies (GWAS) were conducted that led to publications in high-impact journals. Other studies in this research line have included evaluation of improved predictive capacity when risk functions incorporate genetic information. Finally, efforts were made to evaluate the impact on cardiovascular risk of epigenetic variations (DNA modifications that do not include changes in DNA sequencing, basically DNA methylation) and the influence of lifestyle on epigenetic variability.
At present, the primary objectives in this research line are to identify the genetic variants associated with cardiovascular characteristics (myocardial infarction, hypertension and cardiovascular risk factors), to determine the extent to which these variants can increase the predictive capacity of traditional cardiovascular risk functions, and finally, to evaluate the impact of epigenetic variants on cardiovascular characteristics.
DNA methylation and obesity traits: An epigenome-wide association study. The REGICOR study.
Epigenetics 2017 12 (10): 909-916, PMID: 29099282
Burden of risk alleles for hypertension increases risk of intracerebral hemorrhage.
Stroke 2012 Nov; 43 (11): 2877-83, PMID: 22933587
Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma.
Nat. Genet. 2011 Nov; 43 (11): 1131-8, PMID: 22001757
Hundreds of variants clustered in genomic loci and biological pathways affect human height.
Nature 2010 Oct; 467 (7317): 832-8, PMID: 20881960
New susceptibility locus for coronary artery disease on chromosome 3q22.3.
Nat. Genet. 2009 Mar; 41 (3): 280-2, PMID: 19198612
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
Association between ESR2 genetic variants and risk of myocardial infarction.
Clin. Chem. 2008 Jul; 54 (7): 1183-9, PMID: 18487282
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
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
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
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
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
[Paraoxonase 1 gene 192 polymorphism, physical activity and lipoprotein in women].
Med Clin (Barc) 2004 Feb; 122 (4): 126-9, PMID: 14967092
[The antioxidant function of high density lipoproteins: a new paradigm in atherosclerosis].
Rev Esp Cardiol 2004 Jun; 57 (6): 557-69, PMID: 15225502
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
Obesity modulates the association among APOE genotype, insulin, and glucose in men.
Obes. Res. 2003 Dec; 11 (12): 1502-8, PMID: 14694215
Antioxidant paraoxonase 1 activity in the metabolic syndrome.
J. Clin. Endocrinol. Metab. 2003 Nov; 88 (11): 5422-6, PMID: 14602783
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
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
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
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
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
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
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
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
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
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
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