Efthimios Dardiotis1, Vasileios Siokas2, Chrysa Marogianni2, Athina-Maria Aloizou2, Maria Sokratous2, Konstantinos Paterakis3, Maria Dardioti2, Savas Grigoriadis4, Alexandros Brotis3, Eftychia Kapsalaki5, Kostas Fountas3, Jeremiasz Jagiella6, Georgios M Hadjigeorgiou7. 1. Department of Neurology, Laboratory of Neurogenetics, University of Thessaly, University Hospital of Larissa, Larissa, Greece. Electronic address: edar@med.uth.gr. 2. Department of Neurology, Laboratory of Neurogenetics, University of Thessaly, University Hospital of Larissa, Larissa, Greece. 3. Department of Neurosurgery, University of Thessaly, University Hospital of Larissa, Larissa, Greece. 4. Second Department of Neurosurgery, Hippokration University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece. 5. Department of Radiology, University of Thessaly, School of Medicine, Larissa, Greece. 6. Department of Neurology, Medical College Jagiellonian University, Krakow, Poland. 7. Department of Neurology, Laboratory of Neurogenetics, University of Thessaly, University Hospital of Larissa, Larissa, Greece; Department of Neurology, Medical School, University of Cyprus, Nicosia, Cyprus.
Abstract
BACKROUND: A relatively small number of genetic variants are implicated to pathophysiology of intracerebral hemorrhage (ICH). Aquaporin-4 (AQP4) has been reported to be implicated in the pathophysiological processes of ICH development. OBJECTIVE: To examine the role of AQP4 gene region polymorphisms on the ICH risk. METHODS: A total of 250 Greek and 193 Polish patients with primary ICH and 250 and 322 respective controls were enrolled, forming two independent cohorts in order to validate any significant effect. With logistic regression analyses, 7 AQP4 tag single nucleotide polymorphisms (SNPs) were examined for association with ICH risk, lobar/non-lobar ICH risk, and 6-month disability after ICH. Cox regression analysis was applied in order to the effect of AQP4 SNPs on ICH age of onset be tested. Correction for multiple comparisons was applied. RESULTS: Multivariate logistic regression analysis showed that rs3875089 in the Greek cohort and rs3763043, rs335931 in the Polish cohort had a significant influence on the risk of ICH, lobar and non-lobar ICH. Regarding the age of onset, rs3875089 in the Greek cohort and rs3763043, rs11661256 in the Polish cohort were found to significantly alter the age of onset of ICH and its subtypes. However, all of the above associations did not survive the Bonferroni correction (p-value >0.007). Finally, AQP4 tag SNPs were not found to have any significant effect on long-term disability after ICH. CONCLUSIONS: In conclusion, the present study provides an indication that AQP4 gene variants may affect susceptibility to primary ICH and may influence the ICH age of onset.
BACKROUND: A relatively small number of genetic variants are implicated to pathophysiology of intracerebral hemorrhage (ICH). Aquaporin-4 (AQP4) has been reported to be implicated in the pathophysiological processes of ICH development. OBJECTIVE: To examine the role of AQP4 gene region polymorphisms on the ICH risk. METHODS: A total of 250 Greek and 193 Polish patients with primary ICH and 250 and 322 respective controls were enrolled, forming two independent cohorts in order to validate any significant effect. With logistic regression analyses, 7 AQP4 tag single nucleotide polymorphisms (SNPs) were examined for association with ICH risk, lobar/non-lobar ICH risk, and 6-month disability after ICH. Cox regression analysis was applied in order to the effect of AQP4 SNPs on ICH age of onset be tested. Correction for multiple comparisons was applied. RESULTS: Multivariate logistic regression analysis showed that rs3875089 in the Greek cohort and rs3763043, rs335931 in the Polish cohort had a significant influence on the risk of ICH, lobar and non-lobar ICH. Regarding the age of onset, rs3875089 in the Greek cohort and rs3763043, rs11661256 in the Polish cohort were found to significantly alter the age of onset of ICH and its subtypes. However, all of the above associations did not survive the Bonferroni correction (p-value >0.007). Finally, AQP4 tag SNPs were not found to have any significant effect on long-term disability after ICH. CONCLUSIONS: In conclusion, the present study provides an indication that AQP4 gene variants may affect susceptibility to primary ICH and may influence the ICH age of onset.