Genetics

The Big Asthma Lie

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The possibility that genes known to be important in asthma may also be important in obesity is among the most interesting areas of research in this field. Because genes tend to be pleiotropic, it is biologically plausible that genes important in one complex trait could be important in another. Linkage analysis has identified several linkage peaks with chromosomal regions that are shared for obesity and asthma phenotypes (28). Chromosomal areas of 5q, 6p, 11q, and 12q all contain regions with loci common to both complex phenotypes. Chromosome 5q contains the ^-adrenergic receptor gene ADRB2 and the glucocorticoid receptor gene NR3C1. Furthermore, ADRB2 encodes a receptor that influences sympathetic nervous system activity, which is important in controlling both airway tone and metabolic rate. The glucocorticoid receptor is involved in modulating inflammation important in both diseases. Chromosome 6p, which contains the HLA gene cluster and TNF, influences the immune and inflammatory response important in both these conditions. Chromosome 11q13 contains UCP2, UCP3, and the gene encoding the low-affinity immunoglobulin E receptor FCeRB. The uncoupling proteins (encoded by UCP2 and UCP3) influence metabolic rate but have no known function in asthma. The low-affinity immunoglobulin E receptor is part of the T-helper type 2 inflammatory response, which is increased in asthma and has not been assessed for modification by obesity. Chromosome 12q contains the inflammatory cytokine genes STAT6, IGF1, IL1A, and LTA4H. As already noted, inflammation is a feature common to both obesity and asthma. Research needs to be conducted to relate specific genetic polymorphisms in these and other loci to the effects of the obesity phenotype on asthma (28,40,41).

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