Atherosclerosis: From Genetic Polymorphisms to System Genetics
INSERM U525, Paris.Cardiovascular Toxicology (Impact Factor: 1.72). 02/2005; 5(2):143-52. DOI: 10.1385/CT:5:2:143
It is generally considered that the genetics of atherosclerosis and its complications involves a large number of genes with common alleles having weak effects on disease risk but possibly interacting with each other and with non-genetic factors. In such a complex system, absence of marginal effects (effects of polymorphisms considered one at a time) is insufficient to exclude the implication of a polymorphism on disease risk. Investigating polymorphisms and even genes one by one is no longer appropriate. It is necessary to focus on biological systems and integrate the contribution of genetic as well as non-genetic factors and their interactions. Hopefully, system genetics will ultimately improve our understanding of the genetic architecture of complex traits.
- Fitness & Performance Journal 09/2004; 3(5):279-283. DOI:10.3900/fpj.3.5.279.e
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ABSTRACT: Inherited risk factors have been suggested to play an important role in the pathogenesis of vascular complications of inflammatory bowel disease (IBD). The aim of the present study was to investigate the role of mutations associated with cardiovascular disease in IBD patients with or without vascular complications compared with thrombotic and healthy controls (HC). Twelve polymorphisms of thrombophilic and vasoactive genes were evaluated in a group of 30 IBD patients with vascular complications (IBD-VC) compared with 60 IBD patients without vascular complications, 30 thrombotic controls (TC), and 54 healthy controls, using a commercially available kit. No significant differences between IBD-VC and TC concerning the carriage of these mutations were found. The frequencies of the factor V (FV) 506 RQ (Leiden) genotype and the 506Q allele were significantly higher in these groups than in HC (P < 0.05) but not IBD controls (P > 0.05). The allele frequency of the mutant 4G allele of the plasminogen activator inhibitor (PAI) polymorphism, similar in the IBD-VC and TC groups, was significantly higher in these groups compared with the IBD group (P = 0.03) and the HC (P = 0.001). It is noteworthy that there was a trend of association of FV R506Q polymorphism with venous thrombosis and PAI-1 gene polymorphism with arterial thrombosis. Our results suggest that the investigated gene polymorphisms do not differ in patients with IBD-VC and TC. FV R506Q and PAI-1 gene polymorphisms might be associated with the increased risk of development of vascular complications in IBD.Inflammatory Bowel Diseases 04/2007; 13(4):410-5. DOI:10.1002/ibd.20076 · 4.46 Impact Factor
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ABSTRACT: Coronary heart disease (CHD) prevention has largely benefited in the past from the development of epidemiological research. However, the opposition association-causation is currently raised from observational data. We successively review, from some important examples, the classical methodological approach for discussing causality in epidemiology. The easy identification of DNA polymorphisms has prompted new CHD aetiological research in the past 10 years. Causality of the associations presents some special characteristics when genes are involved: necessity of replication, Mendelian randomization..., which might prove to be important in future research.Comptes Rendus Biologies 05/2007; 330(4):299-305. DOI:10.1016/j.crvi.2007.02.016 · 0.98 Impact Factor
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