Variants of the elastin (ELN) gene and susceptibility to intracranial aneurysm: a synthesis of genetic association studies using a genetic model-free approach.
BACKGROUND
The presence of an intracranial aneurysm (IA) is thought to have a genetic origin. The genetic association studies (GAS) that investigated the association between IA and elastin gene (ELN) variants have produced contradictory or inconclusive results.


METHODS
In order to decrease the uncertainty of estimated genetic risk effects, a meta-analysis of published GAS-related variants in the ELN gene (ELN INT20 1315T > C, EX20 1264G > A, INT23 1501 + 24T > C and INT4 196 + 71G > A) with susceptibility to IA was conducted using a genetic model-free approach. The risk effects were estimated using the generalized odds ratio (ORG) metric.


RESULTS
The analysis showed significant association for the INT20 1315T > C variant [ORG = 0.66 (0.45-0.95)], indicating a protection effect. For the variants EX20 1264G > A, INT23 1501 + 24T > C and INT4 196 + 71G > A, no statistically significant association with IAs was found.


CONCLUSIONS
There is evidence that the ELN variant INT20 1315T > C is implicated in the development of IA; however, the results should be interpreted with caution since the number of published studies is limited.
a Department of Neurosurgery , University of Thessaly School of Medicine , Larissa , Greece.
Konstantinos
K
Paterakis
b Vascular Surgery Department , University of Thessaly School of Medicine , Larissa , Greece.
Stelios
S
Koutsias
c Department of Biomathematics , University of Thessaly School of Medicine , Larissa , Greece.
Chrysoula
C
Doxani
c Department of Biomathematics , University of Thessaly School of Medicine , Larissa , Greece.
Paraskevi
P
Xanthopoulou
c Department of Biomathematics , University of Thessaly School of Medicine , Larissa , Greece.
Chrysoula
C
Kokkali
c Department of Biomathematics , University of Thessaly School of Medicine , Larissa , Greece.
Ioanna
I
Mpoulimari
c Department of Biomathematics , University of Thessaly School of Medicine , Larissa , Greece.
Maria
M
Tziastoudi
d Department of Neurosurgery , University Hospitals of Cleveland, St. Vincent's Hospital Manhattan, Weill Cornell Medical College , OH , USA.
Ioannis
I
Karampelas
e Department of Neurology , University of Thessaly School of Medicine , Larissa , Greece.
Efthimios
E
Dardiotis
e Department of Neurology , University of Thessaly School of Medicine , Larissa , Greece.
Georgios
G
Hadjigeorgiou
a Department of Neurosurgery , University of Thessaly School of Medicine , Larissa , Greece.
Alexandros G
AG
Brotis
c Department of Biomathematics , University of Thessaly School of Medicine , Larissa , Greece.|f Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Tufts University School of Medicine , Boston , MA , USA.|g BECRO , Athens , Greece.
Elias
E
Zintzaras
D004549:Elastin / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D002532:Intracranial Aneurysm / Q000235:genetics*
D004549:Elastin
ELN; elastin gene; genetic association; intracranial aneurysm; intracranial hemorrhage; subarachnoid hemorrhage