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Symposium on ’Nutrition in the post-genomic era’ Plenary session 4: Genetic variation and diet-related disease

Gene polymorphisms, inflammatory diseases and cancer

Published online by Cambridge University Press:  05 March 2007

W. Martin Howell*
Affiliation:
Histocompatibility & Immunogenetics Laboratory/Human Genetics Division, Southampton University Hospitals, Southampton SO16 6YD, UK
Philip C. Calder
Affiliation:
Histocompatibility & Immunogenetics Laboratory/Human Genetics Division, Southampton University Hospitals, Southampton SO16 6YD, UK
Robert F. Grimble
Affiliation:
Institute of Human Nutrition, University of Southampton, Southampton SO16 7PX, UK
*
*Corresponding author: Dr W. M. Howell, fax +44 23 8070 1416, email wmh1@soton.ac.uk
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Abstract

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Re´sume´Parmi les ge`nes dont les produits jouent un rle critique dans la re´gulation de la re´ponse immune, on trouve les familles de ge`nes de l'antige`ne leucocyte humain (ALH) et de la cytokine. Les ge`nes ALH sont les plus polymorphes du ge´nome humain, et ce polymorphisme entraine des diffe´rences fonctionnelles des mole´cules ALH exprime´es, qui se traduit par des diffe´rences individuelles dans la manie`re dont des peptides antige´niques se pre´sentent aux cellules T. De plus, un nombre conside´rable de polymorphismes des ge`nes associe´s a la cytokine ont e´te´ identifie´s, la plupart d'entre eux se produisent au niveau du promoteur de ces ge`nes, ce que dans de nombreux cas se traduit par l'expression diffe´rentielle in vitro de leurs respectifs produits ge´ne´tiques pro- ou anti-inflammatoire. Des polymorphismes ALH particuliers aboutirent a` des associations bien de´finies avec un grand nombre de maladies immunologiquement medie´es, parmi lesquelles quelques-unes avec des facteurs de risque die´te´tique. Par exemple, des individus de ge´notype HLA-DQA1*0501, DQB1*0201 ont un risque deux cent fois plus grand de de´velopper une intole´rance au gluten alimentaire (maladie ce´liaque), et des facteurs additionnels en relation avec l'ALH peuvent influencer le de´veloppement d'un lymphome maligne dans une maladie ce´liaque existante. De mme, des alle`les HLA-DRB1 qui partage une se´quence motive commune constituent le premier facteur de risque ge´ne´tique de l'arthrite rhumatode. L'influence de polymorphismes associe´s a une expression de cytokine diffe´rentiel sur la susceptibilite´ aux maladies pre´sent dans ce moment un grand inte´rt. La plupart de l'attention a e´tait centre´ les associations avec la susceptibilite´ de maladies medie´es immunologiquement be´nignes, parmi eux un grand nombre de maladies de l'intestin. Toutefois, un travail re´cent dans notre laboratoire indique que les polymorphismes de la cytokine peuvent influencer la susceptibilite´ a` certains cancers (ainsi que son pronostic), entre eux le me´lanome de peau maligne et des tumeurs solides qui peuvent tre affecte´s par l'alimentation, comme le cancer de prostate (collaboration avec le CRC/BPG e´tude familial du cancer de prostate Royaume-Uni). De plus, des travails pre´liminaires sugge`rent que la modulation par l'alimentation des niveaux d'expression de certaines cytokines dans des sujets humains peut tre de´pendent du ge´notype.

Type
Meeting Report
Copyright
Copyright © The Nutrition Society 2002

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