Translational research : the journal of laboratory and clinical medicine
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Asthma is a complex respiratory disease whose incidence has increased worldwide in the last decade. Currently there is no cure for asthma. Although bronchodilator and anti-inflammatory medications are effective medicines in some asthmatic patients, it is clear that an unmet therapeutic need persists for a subpopulation of individuals with severe asthma. ⋯ Inhibitors of the mevalonate pathway or statins hold promise for asthma treatment, because they exhibit anti-inflammatory, antimigratory, and antiproliferative effects in preclinical and clinical studies, and they can target the smooth muscle. This review will discuss current knowledge of ASM biology and identify gaps in the field to stimulate future investigations of the cellular mechanisms that control ASM overabundance in asthma. Targeting ASM has the potential to be an innovative venue of treatment for patients with asthma.
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The advent of the first wave of genome-wide association studies (GWAS) provided a new conceptual framework in the search for variants underlying common disorders: a massive scan of the genome, free from underlying assumptions for biological or positional candidate loci, genes, and variants. Thus, GWAS have been labeled as a "hypothesis-free" or "agnostic" approach, overcoming the obstacles imposed by the incomplete understanding of disease pathophysiology. ⋯ Dictated by the design of genotyping platforms or the analysis methodologies, the implicit hypotheses of GWAS and their related implications for future research are summarized in this commentary. Since the result of any biological experiment is primarily determined by the extent to which the hypotheses tested truly hold, unless the presumptions of GWAS are acknowledged and complementary genetic analysis methods are implemented, the full advantage of genomic scans of human variation will not be realized.