Background: Mutation T/C inside codon 131 of the gene encoding the alpha subunit of Gs protein (GNAS1) causes the increased activation of adenyl cyclase, which plays an important role in cardiovascular regulation. The aim of the present study was to evaluate GNAS1 T/C,Ile 131 mutation's manifestation in syncopal patients regarding head-up tilt test (HUTT) results.
Methods and results: In 137 syncopal patients (without any other diseases) the silent T/C,Ile 131 mutation within the GNAS1 codon on chromosome 20 q was identified. This mutation consists of the presence (+) or absence (-) of a target site for endonuclease FokI (Promega). Ninety-six patients (70%) with positive HUTT had a higher FokI+ allele frequency compared with those with negative tilting results (49% vs 27%, X(2)=12.05; p<0.001). In positive tilted patients, the studied mutation had significant influence on blood pressure (p<0.05). When comparing positive HUTT with vasodepressore component, cardioinhibition results and negative HUTT, the frequencies of the FokI+ allele were decreased among these groups: 53%, 36% and 27%, respectively.
Conclusions: An association between positive tilting and mutation C/T,Ile 131 within the GNAS1 codon was found. The predisposition to vasovagal syncope seems to be associated with the GNAS1 FokI+ allele.