Hypothesis driven research and molecular mechanisms in functional dyspepsia: the beginning of a beautiful friendship in research and practice?

There is accumulating evidence of a genetic predisposition in at least a subset of patients with functional GI symptoms. Hence, hunting for genes in irritable bowel syndrome and functional dyspepsia has become fashionable of late. Unfortunately, as in other fields, replication of gene association studies has most often been problematic. In this issue of the Journal, independent corroboration of an association of dyspepsia with GNbeta3 is reported. Other carefully selected putative genes including polymorphisms in the alpha2A adrenoreceptor, the serotonin reuptake transporter, and the 5-HT1A receptor were not associated. The study raises three key questions all considered in this editorial: (a) if GNbeta3 is truly associated with functional and uninvestigated dyspepsia, why might this be the case, (b) what molecular mechanisms may be of most relevance, and (c) perhaps most importantly, does or will this finding translate into clinical practice in terms of diagnosis or treatment? New knowledge of gene associations like GNbeta3 and their pathophysiological relevance may ultimately lead to better targeted therapy as well as new disease modifying treatments.