The intracranial aneurysm susceptibility genes HSPG2 and CSPG2 are not associated with abdominal aortic aneurysm.
BACKGROUND
A genetic variant on chromosome 9p21 associates with abdominal aortic aneurysm (AAA) and intracranial aneurysm (IA), indicating that despite the differences in pathology there are shared genetic risk factors. We investigated whether the IA susceptibility genes heparan sulfate proteoglycan 2 (HSPG2) and chondroitin sulfate proteoglycan 2 (CSPG2) associate with AAA as well.


METHODS
Using tag single nucleotide polymorphisms (SNPs), all common variants were analyzed in a Dutch AAA case-control population in a 2-stage genotyping approach. In stage 1, 12 tag SNPs in HSPG2 and 22 tag SNPs in CSPG2 were genotyped in 376 patients and 648 controls. Genotyping of significantly associated SNPs was replicated in a second independent cohort of 360 cases and 376 controls.


RESULTS
In stage 1, no HSPG2 SNPs and 1 CSPG2 SNP associated with AAA (rs2652106, P = .019). Association of this SNP was not replicated (P = .342).


CONCLUSIONS
Our findings demonstrate that, in contrast to IA, HSPG2 and CSPG2 do not associate with AAA.
Baas
Annette F
AF
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, the Netherlands. a.f.baas@umcutrecht.nl
Medic
Jelena
J
van't Slot
Ruben
R
de Vries
Jean-Paul P M
JP
van Sambeek
Marc R H M
MR
Verhoeven
Eric L G
EL
Boll
Bart P
BP
Grobbee
Diederick E
DE
Wijmenga
Cisca
C
Blankensteijn
Jan D
JD
Ruigrok
Ynte M
YM
D000368:Aged; D000369:Aged, 80 and over; D017544:Aortic Aneurysm, Abdominal / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D019812:Heparan Sulfate Proteoglycans / Q000235:genetics*; D006801:Humans; D002532:Intracranial Aneurysm / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D053675:Versicans / Q000235:genetics*
D016326:Extracellular Matrix Proteins; D019812:Heparan Sulfate Proteoglycans; C508322:VCAN protein, human; D053675:Versicans; C071927:perlecan