[Current opinions about asthma: genetic factors].
Asthma is a common disease which prevalence has been rising over the last years. It is therefore not a surprise that researchers have tried to set up genetics study in order to better understand the disease and hopefully find new ways for treatment and possibly prevention. Asthma has been found to run in families in many studies. Recently evidence has been gained that it segregates in families, when assessed by several phenotypes like atopy and hyperresponsiveness. Moreover, studies have shown that the inheritance of high levels of total serum IgE, a marker of atopy, are better fitted in a segregation analysis when a two locus model was applied than when a one locus model was applied. This suggests that more than one gene is involved in this complex disease. The search for genes in asthma has now led to several locations on the genome, including genes on chromosome 5, 11 and 12. The latter chromosomal regions have been replicated in several studies. Not all studies show these positive linkages, which may due to family selection, the number of families under study, the definition of the asthma phenotype under study and the prevalence of the phenotype in the general population. Apart from a genome wide search, several groups have looked for specific regions of interest, like the Fc epsilon receptor for IgE on chromosome 11 and the cluster of cytokines on chromosome 5q. Association studies have shown that several polymorphisms in chromosomal regions are linked to atopy, hyperresponsiveness and asthma. Data today suggest that several genes will be involved and current knowledge points at the possibilities for genetic analyses to further unravel asthma subtypes, like severe asthma, aspirin-sensitive asthma etc. A polymorphism in the beta-receptor has recently been found to be associated with nocturnal asthma. Moreover, polymorphisms in this receptor are also more prevalent in patients who respond less to beta-agonist therapy. A recent observation that a polymorphism in the 5-Lipoxygenase gene is linked to less responsiveness to a leukotrien-antagonist shows that the future perspectives of genetic studies may lie also in revealing the chromosomal map of the best therapy for an individual patient with asthma. Although, this may sound far fetched, it will become within our reach in the future. Finally, gene-environment interaction will be of interest for further prevention of asthma.
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Afdeling Longziekten-A. Z. Groningen.
D000595:Amino Acid Sequence; D001249:Asthma / Q000235:genetics* / Q000276:immunology; D002874:Chromosome Mapping; D002877:Chromosomes, Human; D006801:Humans; D007073:Immunoglobulin E / Q000235:genetics; D008969:Molecular Sequence Data; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D014409:Tumor Necrosis Factor-alpha; D007073:Immunoglobulin E