Genetic insight into syncopal tilted population with severe clinical presentation.
An impairment of cardiovascular reflexes may be the result of functional alterations in the G proteins intracellular signaling produced by functional genes' polymorphisms. The aim was to evaluate the relationships between single nucleotide polymorphisms in genes encoding G-proteins signaling pathways and syncopal patients with severe clinical manifestation.


RESULTS
From 307 syncopal patients free from any other diseases 83 (27%) had at least one malignant episode of syncope with a significant injury as fractures. There was 1.9 malignant spells per patient. All patients were tilted and genotyped by polymerase chain reaction followed by restriction fragment length polymorphism method. 74 healthy volunteers with negative history of syncope constituted the control group were also genotyped. Following polymorphisms were detected: C393T in gene encoding the alfa-subunit of Gs-protein (GNAS1), C825T of gene for G-protein beta 3 subunit (GNB3) and C1114G for the gene of cardiac regulator of G-protein signaling (RGS2). We found an association with lower risk of malignant syncope in positive tilting patients during passive phase of the test compared to NTG-enhanced (OR 0.38; 95% CI 0.15-0.95; P=0.04). No difference between healthy controls and patients in the alleles frequency was found (P>0.05). Neither the 393T allele of GNAS1 and 825T allele of GNB3 nor 1114G allele of RGS2 was associated with enhanced risk of severe clinical manifestation (P>0.05).


CONCLUSIONS
The studied single nucleotide polymorphisms of genes encoding G-proteins signaling pathways seem to be not connected with the severe clinical manifestation of syncope.
Lelonek
Malgorzata
M
Department of Cardiology, Chair of Cardiology and Cardiac Surgery, Medical University of Lodz, Poland. mlelonek@poczta.fm
Pietrucha
Tadeusz
T
Matyjaszczyk
Monika
M
Goch
Jan Henryk
JH
D000328:Adult; D001342:Autonomic Nervous System Diseases / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D002864:Chromogranins; D004252:DNA Mutational Analysis; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics; D019204:GTP-Binding Proteins / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D020710:RGS Proteins / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D019462:Syncope, Vasovagal / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D055815:Young Adult
D002864:Chromogranins; C454420:G-protein beta3 subunit; D020710:RGS Proteins; C087182:RGS2 protein, human; C406732:GNAS protein, human; D019204:GTP-Binding Proteins; D019205:GTP-Binding Protein alpha Subunits, Gs; D020962:Heterotrimeric GTP-Binding Proteins