Genes involved in the transforming growth factor beta signalling pathway and the risk of intracranial aneurysms.
OBJECTIVE
The 19q13.3 locus for intracranial aneurysms (IA) partly overlaps with the 19q13 locus for abdominal aortic aneurysms (AAA). A common genetic risk factor located in this locus for the two aneurysm types seems plausible. The transforming growth factor beta (TGF-beta) signalling pathway plays a role in aortic aneurysms but may also play a role in aneurysms in general. In the combined region of the 19q13 loci for IA and AAA we identified two candidate genes that are both involved in the TGF-beta signalling pathway: hepsin (HPN) and the latent transforming growth factor beta-binding protein 4 (LTBP4). We hypothesised that single nucleotide polymorphisms (SNP) in the HPN and LTBP4 genes are associated with IA.


METHODS
We analyzed all the common variations using tag SNP in the HPN and LTBP4 genes for association with IA in 390 patients and 642 controls in the Dutch population. Six tag SNP in the HPN gene and five tag SNP in the LTBP4 gene were genotyped.


RESULTS
No differences in SNP frequency were observed for both the HPN and LTBP4 gene between patients and controls.


CONCLUSIONS
Our findings suggest that variations in or near the HPN and LTBP4 genes do not play a role in the susceptibility to IA in the Dutch population.
Ruigrok
Y M
YM
Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands. ij.m.ruigrok@umcutrecht.nl
Tan
S
S
Medic
J
J
Rinkel
G J E
GJ
Wijmenga
C
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017542:Aneurysm, Ruptured / Q000175:diagnosis / Q000235:genetics*; D017544:Aortic Aneurysm, Abdominal / Q000235:genetics*; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D002532:Intracranial Aneurysm / Q000175:diagnosis / Q000235:genetics*; D053779:Latent TGF-beta Binding Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012697:Serine Endopeptidases / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D013345:Subarachnoid Hemorrhage / Q000175:diagnosis / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics*
C509040:LTBP4 protein, human; D053779:Latent TGF-beta Binding Proteins; D016212:Transforming Growth Factor beta; D012697:Serine Endopeptidases; C055645:hepsin