Functional Dyspepsia, 2016

Nicholas J. Talley; Marjorie M. Walker; Gerald Holtmann


Curr Opin Gastroenterol. 2016;32(6):467-473. 

In This Article


The role of genes in functional dyspepsia remains to be clarified, although a genetic predisposition remains strongly suspected. Singh et al.[12] report new evidence that the single nucleotide polymorphism C825T in the G-protein beta polypeptide-3 gene (GNbeta3), which widely modulates signal transduction depending on whether it is homozygous (CC or TT) or heterozygous (CT), is associated with functional dyspepsia. In 237 functional dyspepsia patients compared with controls, the TT polymorphism was associated with functional dyspepsia in this Indian study. On the other hand, a meta-analysis[13] comprising 12 studies (1109 cases versus 2853 controls) concluded that the single nucleotide polymorphism GNbeta3 was not linked to functional dyspepsia, reflecting the heterogeneity of the literature. Singh et al.[12] also evaluated the cholecystokinin-A-receptor gene polymorphism (CCK-AR) in functional dyspepsia, as CCK is a key satiety regulator and early satiety is a key symptom in functional dyspepsia, and found that the CC homozygote was protective, although surprisingly this was not functional dyspepsia subtype-specific. The major problem with these gene association studies is that all were underpowered for what are likely weak associations, and a lack of positive verification studies for identified gene targets plagues the field.