The Hereditary Basis of Allergic Diseases

Allergic diseases are complex and involve a range of environmental factors interacting with a susceptible genotype. The familial clustering of diseases, such as asthma and hay fever, has been recognised for over two centuries, but identification of the genetic basis to this had to await the molecular biological revolution. Estimates of the contribution that genetic factors make to asthma susceptibility range from 35% to 70%. For the majority of allergic diseases, segregation analysis has not identified a consistent Mendelian pattern of inheritance, which, when combined with multiple phenotypes and environmental interactions, has made identifying candidate genes especially difficult and, at times, controversial. Part of the difficulty has been lack of agreement over phenotype definitions, reduced power of studies to predict linkage and association, and, importantly, lack of true heterogeneity between populations. Despite these difficulties, the last decade has witnessed enormous progress in this field.

Includes supplementary material: sn.pub/extras

Auteur
Prof. Stephen Holgate, MRC Clinical Professor of Immunopharmacology, Division of Respiratory Cell and Molecular Biology, University of Southhampton School of Medicine. Applying basic science to the clinical interface in allergy and asthma has been the guiding principle of Prof. Stephen Holgate's career. This has involved him in environmental and genetic epidemiology, physiology, cell and molecular biology of disease processes as they occur in humans. An AAAAI member since 1986 and Fellow from 1993, Professor Holgate has been active in the field of allergy and immunology both in the United Kingdom and overseas and in 2001 received the Academy's Honorary Fellow Award. He was President of the British Society of Allergy and Clinical Immunology (BSACI) from 1990-93 and the Robert Cook Memorial Lecturer in 1995 and 2000. He received the RCP London Graham Bull Prize for research and was elected an honorary member of the Association of Physicians in UK and Ireland following the delivery of the Sir William Osler Lecture in 2003. He has been an active contributor to the Collegium Internationale Allergologicum since 1990. Professor Holgate is a member of the Infection, Inflammation and Repair Division in the School of Medicine, University of Southampton at Southampton General Hospital, UK and since 1987 has held a Medical Research Council (MRC) Clinical Professorship. He received his undergraduate medical training at Charing Cross Hospital, London and specialised in respiratory medicine and allergy. He holds Fellowships from the Royal Colleges of Physicians, Pathologists, Institute of Biology and Academy of Medical Sciences. He is a member of the Royal Commission on Environmental Pollution and has been a censor of the Royal College of Physicians. He has served on a number of Government Committees including the Sub-committee for Efficacy and Adverse Drug Reactions of the CSM (SEAR), MRC Project Grant Committee, Systems Board, Cross Board Group and most recently Councils Subcommittee on Corporate Policy and Evaluation (SCoPE), its Clinical Research Oversight Group (CROG) and is Chairman of Councils new Subcommittee on Evaluation (SOE). He has been Chairman of the UK Department of Health Committee on the Medical Effects of Air Pollution and has been appointed as Chairman of the UK Government (DEFA) Expert Panel on Air Quality Standards and Chairman of the Science Council's Science in Health Group. He has been a member of the Royal Commission of Environmental Pollution since 2002. He serves as a member of the Board of Directors for the World Allergy Organization (WAO). Professor Holgate's wwork has been recognised with a Scientific Achievement Award of the IAACI in 1994, the Rhone-Poulenc Rorer World Health Award in 1995, the King Faisal International Prize in Medicine in 1999 and Doctorates Hon Causa at University of Ferrara, Italy and Jagellonian University, Krakow, Poland in 1997 and 1999 respectively. He was elected to the Polish Academy of Arts and Science in 2001, received the Royal Society of Medicine Ellison Cliffe Medal in 2003 and the University of Ghent Gold Medal for Achievement in Clinical Science in 2004. According to the ISI Prof. Holgate was 8th most frequently cited author between 1990-2000 in the field of Biomedical Sciences in the United Kingdom and in 2002 became a member of ISI's most highly cited researcher databas.

Contenu
Heredity of allergy and asthma 1.- Genome scans for asthma.- The role of founder populations in mapping complex disease genes: Studies in the South Dakota Hutterites.- Genetic regulation of specific IgE responsiveness.- Genetic variation at the HLA and TCR loci and the development of allergy and asthma.- Chromosome 11q13, FccRI13 and atopic asthma.- Genetic regulation of interleukin-13 production.- The role of interleukin-9 and the interleukin-9 receptor gene candidates in asthma.- Genetics of the nitric oxide synthetic pathway in asthma.- Genetic regulation of leukotriene production and activity.- Genetics of asthma severity.