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mercredi 14 mars 2012

Infarctus du myocarde: génomique, risque et médecine personnalisée



Nous savons tous que les voies qui conduisent à l'athérome sont multiples mais il semble que la voie finale commune soit l'inflammation
Chez la majorité c'est le tabac qui est le facteur principal de cette inflammation.
Cumulative risk of coronary heart disease (baseline age 40 years)
Curves for smokers (—○—) and non-smokers (—▪—)with UK population mean values for total and HDL-cholesterol and blood pressure (BP). Curves for non-smokers, with systolilc BP 8 mm hg below population average (—▿—), for non-smokers with total cholesterol 20% below population average (—⧫—), and non-smokers in whom both systolic BP and total cholesterol are 8 mm hg and 20% (respectively) below population averages (—•—). Curve for a high-risk individual: smoker with systolic BP of 170 mm hg, total cholesterol 7·5 mmol/L, and HDL-cholesterol 0·8 mmol/L (—□—).
Chez certains patients les facteurs de risque classique ne sont pas retrouvés. On invoque alors des prédispositions génétiques. Mais il s'agit toujours de prédispositions à l'inflammation chronique:
"Taken together, these findings suggest that downregulation of adaptive immunity in carriers of haplogroup I is accompanied by upregulation of pathways underlying inflammatory response."
Dans ce contexte regardons les faits. De combien la présence de l'haplotype I sur le chromosome Y augmente-t-il le risque?
"A combined analysis of the age-adjusted eff ects from the BHF-FHS study and WOSCOPS cohort showed that on average haplogroup I increased the risk of coronary artery disease by about 50% (OR 1·56, 95% CI 1·24–1·97, p=0·0002)."
Vous avez bien lu 56%. Ce qui signifie qu'en risque absolu c'est une variation faible sur une population mais qui explique certains des cas où l'infarctus survient sans les facteurs de risque habituels.

Médecine évolutionniste: la base de la compréhension de ces prédispositions génétiques
"Evolutionarily, the distinguishing feature of haplo -
group I is its almost complete absence in indigenous
populations outside Europe.2 The carriers of this
haplogroup probably arrived from the Middle East as
hunter-gatherers during the Paleolithic era roughly
25 000 years ago and it has been suggested that they
spread throughout Europe together with diff usion of the
Gravettian archaeological culture.41 The gradual Neolithic
expansion of farmers 10 000 years ago led to the present
dominance of R1b1b2 (over I and other MSY haplogroups)
in most parts of northern and western Europe.2,42 The
present geographical distribution of one of the major
lineages of haplogroup I (I1) in western Europe correlates
with the well established north–south gradient in
prevalence of coronary artery disease. Indeed, in northern
populations (Scandinavia, Germany, Netherlands) in
which the prevalence of haplogroup I ranges between
15% and 40%, mortality from coronary artery disease is
signifi cantly higher than in southern Europe (France,
Apennine peninsula, Spain, and Switzerland), where
haplogroup I is less prevalent (3–15%).43,44 The north–
south gradient in coronary artery disease morbidity was
also reported in the UK (2011)."

Conseils nutritionnels
Le régime paléo et tout particulièrement le régime anti-inflammatoire sont adaptés. ils peuvent aussi moduler l'expression génique (épigénétique).


Référence
1/ Inheritance of coronary artery disease in men: an analysis of the role of the Y chromosome
Fadi J Charchar, Lisa D S Bloomer, Timothy A Barnes, Mark J Cowley, Christopher P Nelson, Yanzhong Wang, Matthew Denniff , Radoslaw Debiec,
Paraskevi Christofi dou, Scott Nankervis, Anna F Dominiczak, Ahmed Bani-Mustafa, Anthony J Balmforth, Alistair S Hall, Jeanette Erdmann,
Francois Cambien, Panos Deloukas, Christian Hengstenberg, Chris Packard, Heribert Schunkert, Willem H Ouwehand, Ian Ford, Alison H Goodall,
Mark A Jobling, Nilesh J Samani, Maciej Tomaszewski

Lancet 2012; 379: 915–22
2/ http://www.genome.jp/kegg/ 
3/ 
http://dysnutrition.blogspot.com/2009/08/le-cocktail-anti-inflammatoire-naturel.html 
4/ 
http://dysnutrition.blogspot.com/2010/09/noubliez-pas-les-omegas-3-longue-chaine.html

En rouge les voies activées et en bleu celles qui sont freinées; à retenir: la complexité!

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