A novel approach to syncopal patients: association analysis of polymorphisms in G-protein genes and tilt outcome.
OBJECTIVE
G-proteins signal transduction pathways play a basic role in cardiovascular reflexes. We hypothesized that the predisposition to reflex-mediated syncope may be associated with genetic variations in G-protein genes. The aim of this study was to evaluate the effect of three single-nucleotide polymorphisms in G-protein genes on tilting outcome in syncopal patients.


RESULTS
A total of 217 syncopal patients free from any other disease were genotyped and examined related to tilting results. Genotyping was performed by polymerase chain reaction followed by restriction fragment length polymorphism in gene encoding the Gs-protein alpha-subunit (polymorphism C393T), the G-protein beta 3 subunit--GNB3 (polymorphism C825T)--and for the cardiac regulator of G-protein signalling RGS2 (polymorphism C1114G). In multivariate logistic regression analysis, the homozygotes 825TT GNB3 (OR 0.37; 95% CI 0.14-0.97; P < 0.05) and body mass index (OR 0.87; 95% CI 0.78-0.97; P = 0.005) were independently associated with a lower chance of positive tilting results. No relationship was found between Vasovagal Syncope International Study type of syncope and the studied genotypes or the carriage of the polymorphic alleles.


CONCLUSIONS
An association between tilting results and C825T GNB3 polymorphism in syncopal patients was found. The syncopal homozygotes 825TT GNB3 had a significantly lower chance of syncope during tilt testing.
Lelonek
Malgorzata
M
Department of Cardiology, Medical University of Lodz, Sterling Str. 1/3, 91-425 Lodz, Poland. mlelonek@poczta.fm
Pietrucha
Tadeusz
T
Matyjaszczyk
Monika
M
Goch
Jan Henryk
JH
D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D011044:Poland / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D015203:Reproducibility of Results; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D012680:Sensitivity and Specificity; D013575:Syncope / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D018667:Tilt-Table Test / Q000706:statistics & numerical data*; D055815:Young Adult
D019204:GTP-Binding Proteins