Angiotensin-converting enzyme tag single nucleotide polymorphisms in patients with intracerebral hemorrhage.
OBJECTIVE
Studies investigating the association between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and the risk of intracerebral hemorrhage (ICH) have provided conflicting results. Moreover, it is possible that the ACE I/D polymorphism may not represent the functional variant of the gene. The objective of this study was to clarify the influence of the ACE gene region on the risk of ICH by genotyping tag polymorphisms along ACE gene in two independent ethnically different cohorts.


METHODS
We included 250 Greek and 169 Polish unrelated patients with ICH and 250 Greek and 322 Polish normal controls in the study. To cover the majority of the genetic variability across the extended ACE gene region, we identified five tag single nucleotide polymorphisms (rs4343, rs4461142, rs7221780, rs8066276, rs8066114) from the HapMap using a pairwise tagging approach and an r2 greater than or equal to 0.8. Single nucleotide polymorphisms and haplotypes were analyzed for associations with ICH risk, ICH subtype (lobar/nonlobar), and age of disease onset using logistic and Cox regression models. Correction for multiple comparisons was carried out.


RESULTS
In the Polish cohort, we observed a trend toward an association between the rs4461142 and the age of ICH onset (hazard ratio 0.50, 95% confidence interval 0.27-0.90, P=0.02). A common haplotype (GTCTC) also showed a trend for increased ICH risk in the Polish cohort (odds ratio 0.19, 95% confidence interval 0.04-0.85, P=0.02). These results were not replicated in the Greek cohort.


CONCLUSIONS
Our results did not provide clear evidence for a role of ACE gene in the development of ICH.
Department of Neurology, Laboratory of Neurogenetics, University of Thessaly, University Hospital of Larissa, Larissa, Greece.
Efthimios
E
Dardiotis
Jeremiasz
J
Jagiella
Georgia
G
Xiromerisiou
Maria
M
Dardioti
Christina
C
Vogiatzi
Andrzej
A
Urbanik
Konstantinos
K
Paterakis
Apostolos
A
Komnos
Kostas N
KN
Fountas
Agnieszka
A
Slowik
Georgios M
GM
Hadjigeorgiou
D000368:Aged; D000483:Alleles; D002543:Cerebral Hemorrhage / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D054643:INDEL Mutation; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors
D007703:Peptidyl-Dipeptidase A