Publications by authors named "Maria Dardioti"

13 Publications

  • Page 1 of 1

Effect of integrin AV and B8 gene polymorphisms in patients with traumatic brain injury.

Brain Inj 2019 29;33(7):836-845. Epub 2019 Apr 29.

a Department of Neurology, Laboratory of Neurogenetics , University of Thessaly, University Hospital of Larissa , Larissa , Greece.

Α few genetic variants are associated with the outcome after traumatic brain injury (TBI). Integrins are glycoprotein receptors that play an important role in the integrity of microvasculature of the brain. To examine the role of integrin-AV () and integrin-B8 () tag single nucleotide polymorphisms (SNPs) on the outcome of patients with TBI. 363 participants were included and genotyped for 11 SNPs for and 11 for gene. SNPs were tested for associations with the 6-month outcome after TBI, the presence of a hemorrhagic event after TBI, and the initial TBI severity after adjustment for TBI's main predictors. The ITGAV CC and GG genotypes were associated with an unfavorable outcome after TBI, compared to the TT and AA genotypes, respectively. The ITGB8 CC and CC genotypes were associated with increased risk of any cerebral hemorrhagic event after TBI compared to GG and TT respectively. The ITGAV and were associated with the TBI's initial severity. ITGAV gene SNPs may be implicated in the outcome after TBI, as well as in the initial TBI severity, and also of ITGB8 gene SNPs in the risk of hemorrhagic event after a TBI.
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http://dx.doi.org/10.1080/02699052.2019.1606444DOI Listing
April 2020

AQP4 tag SNPs in patients with intracerebral hemorrhage in Greek and Polish population.

Neurosci Lett 2019 03 19;696:156-161. Epub 2018 Dec 19.

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.

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.
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http://dx.doi.org/10.1016/j.neulet.2018.12.025DOI Listing
March 2019

Replication study of GWAS risk loci in Greek multiple sclerosis patients.

Neurol Sci 2019 Feb 26;40(2):253-260. Epub 2018 Oct 26.

Department of Neurology, Laboratory of Neurogenetics, University Hospital of Larissa, University of Thessaly, Larissa, Greece.

Objectives: To validate in an ethnically homogeneous Greek multiple sclerosis (MS) cohort, genetic risk factors for the disease, identified through a number of previous multi-ethnic genome-wide association studies (GWAS).

Methods: A total of 1228 MS cases and 1014 controls were recruited in the study, from 3 MS centers in Greece. We genotyped 35 susceptibility SNPs that emerged from previous GWAS or meta-analyses of GWAS. Allele and genotype single locus regression analysis, adjusted for gender and site, was performed. Permutation testing was applied to all analyses.

Results: Six polymorphisms reached statistical significance (permutation p value < 0.05). In particular, rs2760524 of LOC105371664, near RGS1 (permutation p value 0.001), rs3129889 of HLA-DRA, near HLA-DRB1 (permutation p value < 1.00e-04), rs1738074 of TAGAP (permutation p value 0.007), rs703842 of METTL1/CYP27B1 (permutation p value 0.008), rs9596270 of DLEU1 (permutation p value < 1.00e-04), and rs17445836 of LincRNA, near IRF8 (permutation p value 0.001) were identified as susceptibility risk factors in our group.

Conclusion: The current study replicated a number of GWAS susceptibility SNPs, which implies that some similarities between the examined Greek population and the MS genetic architecture of the GWAS populations do exist.
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http://dx.doi.org/10.1007/s10072-018-3617-6DOI Listing
February 2019

CpG Island Methylation Patterns in Relapsing-Remitting Multiple Sclerosis.

J Mol Neurosci 2018 Mar 7;64(3):478-484. Epub 2018 Mar 7.

Department of Neurology, Laboratory of Neurogenetics, University of Thessaly, University Hospital of Larissa, Biopolis, Mezourlo Hill, 41100, Larissa, Greece.

DNA methylation may predispose to multiple sclerosis (MS), as aberrant methylation in the promoter regions across the genome seems to underlie several processes of MS. We have currently determined the methylation status of eight genes in relapsing-remitting MS patients. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) was used to determine the status of 31 CpG islands, located across eight genes, in 33 healthy individuals and 66 MS patients (33 in relapse and 33 in remission). The methylation levels in the examined sites ranged from 0 to 31%. Methylation positivity for RUNX3 and CDKN2A differed significantly between MS patients and healthy controls. Maximum methylation in RUNX3, CDKN2A, SOCS1, and NEUROG1 genes was significantly different between patients and controls. Roc curves demonstrated that the appropriate cut-offs to distinguish patients from healthy controls were 2% for RUNX3 (OR 3.316, CI 1.207-9.107, p = 0.024) and 3% for CDKN2A (OR 3.077, CI 1.281-7.39, p = 0.018). No difference in methylation was observed between patients in relapse and patients in remission, in any of the genes examined. Methylation patterns of RUNX3 and CDKN2A may be able to distinguish between MS patients and healthy controls, but not between MS patients in relapse and in remission. Graphical Abstract Methylation patterns of RUNX3 and CDKN2A may be able to discriminate healthy individuals from MS patients.
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http://dx.doi.org/10.1007/s12031-018-1046-xDOI Listing
March 2018

A novel mutation in TREM2 gene causing Nasu-Hakola disease and review of the literature.

Neurobiol Aging 2017 05 20;53:194.e13-194.e22. Epub 2017 Jan 20.

Department of Neurology, University of Thessaly, University Hospital of Larissa, Larissa, Greece; Laboratory of Neurogenetics, University of Thessaly, University Hospital of Larissa, Larissa, Greece. Electronic address:

Nasu-hakola disease (NHD) is a rare disease characterized by bone cysts and fractures, frontal lobe syndrome, and progressive presenile dementia. NHD may be the prototype of primary microglial disorders of the CNS or, as they have been coined, "microgliopathies". Mutations in TREM2 and TYROBP genes are known to cause NHD. Interestingly, recent evidence-associated rare genetic variants of TREM2 gene with increased risk of Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis, and Parkinson's disease. Here, we report a 33-year-old Greek female with phenotype suggestive of NHD. Full gene sequencing of the TREM2 and TYROBP genes revealed a novel mutation in exon 2 of TREM2 gene, namely c.244G>T (p.W50C) and heterozygosity in the parents and her brother. This report extends the range of TREM2 mutations that cause NHD phenotype. In addition, we provide a comprehensive review of all reported in the literature TREM2 gene mutations and the respective wide spectrum of clinical manifestations that highlights the importance of considering TREM2 gene mutations in a variety of neurodegenerative phenotypes.
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http://dx.doi.org/10.1016/j.neurobiolaging.2017.01.015DOI Listing
May 2017

Integrins AV and B8 Gene Polymorphisms and Risk for Intracerebral Hemorrhage in Greek and Polish Populations.

Neuromolecular Med 2017 Mar 30;19(1):69-80. Epub 2016 Jul 30.

Laboratory of Neurogenetics, Department of Neurology, Faculty of Medicine, University of Thessaly, University Hospital of Larissa, Biopolis, Mezourlo Hill, 41100, Larissa, Greece.

Α limited number of genetic variants have been linked to the development of intracerebral hemorrhage (ICH). Ιntegrin AV and/or B8-deficient mice were found to develop ICH. The present candidate gene association study was designed to investigate possible influence of integrin AV (ITGAV) and integrin B8 (ITGB8) gene region polymorphisms on the risk of ICH. 1015 participants (250 Greek and 193 Polish patients with primary ICH and 250 Greek and 322 Polish controls) were included in the study. Using logistic regression analyses, 11 tag single nucleotide polymorphisms (SNPs) for ITGAV and 11 for ITGB8 gene were tested for associations with ICH risk, lobar ICH risk and non-lobar ICH after adjustment for age, gender, history of hypertension and country of origin. Linear regression models were used to test the effect of tag SNPs on the ICH age of onset. Correction for multiple comparisons was carried out. The rs7565633 tag SNP of the ITGAV gene was independently associated with the risk of lobar ICH in the codominant model of inheritance [odds ratio (95 % confidence interval (CI)) 0.56 (0.36-0.86), p = 0.0013]. Furthermore, heterozygous individuals of the rs10251386 and the rs10239099 of the ITGB8 gene had significantly lower age of ICH onset compared to the wild-type genotypes [regression coefficient (b) -3.884 (95 % CI -6.519, -1.249), p = 0.0039 and b = -4.502 (95 % CI -7.159, -1.845), p = 0.0009, respectively]. The present study provides preliminary indication for an influence of ITGAV gene tag SNP in the development of lobar ICH and of ITGB8 gene variants in the age of ICH onset.
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http://dx.doi.org/10.1007/s12017-016-8429-3DOI Listing
March 2017

Effect of angiotensin-converting enzyme tag single nucleotide polymorphisms on the outcome of patients with traumatic brain injury.

Pharmacogenet Genomics 2015 Oct;25(10):485-90

aLaboratory of Neurogenetics, Department of Neurology bDepartment of Neurosurgery, Faculty of Medicine, University Hospital of Larissa, University of Thessaly cIntensive Care Unit, General Hospital of Larissa dDepartment of Radiology, School of Medicine, University of Thessaly, Larissa eSecond Department of Neurology, School of Medicine, 'Attikon' University Hospital, University of Athens, Athens fSecond Department of Neurosurgery, Hippokration University Hospital gDepartment of Physiology, Aristotle University of Thessaloniki, Thessaloniki, Greece hInternational Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic.

Background: Genetic variants appear to influence, at least to some degree, the extent of brain injury and the clinical outcome of patients who have sustained a traumatic brain injury (TBI). Angiotensin-converting enzyme (ACE) is a zinc metallopeptidase that is implicated in the regulation of blood pressure and cerebral circulation. ACE gene polymorphisms were found to regulate serum ACE enzyme activity.

Objective: The present study aimed to investigate possible influence of ACE gene region variants on patients' outcome after TBI.

Patients And Methods: In total, 363 TBI patients prospectively enrolled in the study were genotyped for five tag single nucleotide polymorphisms (SNPs) across the ACE gene. Using logistic regression analyses, tag SNPs and their constructed haplotypes were tested for associations with 6-month Glasgow Outcome Scale scores, after adjustment for age, sex, Glasgow Coma Scale scores at admission, and the presence of a hemorrhagic event in the initial computed tomography scan.

Results: Significant effects on TBI outcome were found for three neighboring tag SNPs in the codominant (genotypic) model of inheritance [rs4461142: odds ratio (OR) 0.26, 95% confidence interval (CI) 0.12-0.57, P = 0.0001; rs7221780: OR 2.67, 95% CI 1.25-5.72, P = 0.0003; and rs8066276: OR 3.82, 95% CI 1.80-8.13, P = 0.0002; for the heterozygous variants compared with the common alleles]. None of the constructed common tag SNPs haplotypes was associated with TBI outcome.

Conclusion: The present study provides evidence of the possible influence of genetic variations in a specific region of the ACE gene on the outcome of TBI patients. This association may have pharmacogenetic implications in identifying those TBI patients who may benefit from ACE inhibition.
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http://dx.doi.org/10.1097/FPC.0000000000000161DOI Listing
October 2015

AQP4 tag single nucleotide polymorphisms in patients with traumatic brain injury.

J Neurotrauma 2014 Dec 10;31(23):1920-6. Epub 2014 Oct 10.

1 Department of Neurology, Laboratory of Neurogenetics, University of Thessaly , University Hospital of Larissa, Larissa, Greece .

Accumulating evidence suggests that the extent of brain injury and the clinical outcome after traumatic brain injury (TBI) are modulated, to some degree, by genetic variants. Aquaporin-4 (AQP4) is the predominant water channel in the central nervous system and plays a critical role in controlling the water content of brain cells and the development of brain edema after TBI. We sought to investigate the influence of the AQP4 gene region on patient outcome after TBI by genotyping tag single nucleotide polymorphisms (SNPs) along AQP4 gene. A total of 363 patients with TBI (19.6% female) were prospectively evaluated. Data including the Glasgow Coma Scale (GCS) scores at admission, the presence of intracranial hemorrhage, and the 6-month Glasgow Outcome Scale (GOS) scores were collected. Seven tag SNPs across the AQP4 gene were identified based on the HapMap data. Using logistic regression analyses, SNPs and haplotypes were tested for associations with 6-month GOS after adjusting for age, GCS score, and sex. Significant associations with TBI outcome were detected for rs3763043 (OR [95% confidence interval (CI)]: 5.15 [1.60-16.5], p=0.006, for recessive model), rs3875089 (OR [95% CI]: 0.18 [0.07-0.50] p=0.0009, for allele difference model), and a common haplotype of AQP4 tag SNPs (OR [95% CI]: 2.94, [1.34-6.36], p=0.0065). AQP4 tag SNPs were not found to influence the initial severity of TBI or the presence of intracranial hemorrhages. In conclusion, the present study provides evidence for possible involvement of genetic variations in AQP4 gene in the functional outcome of patients with TBI.
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http://dx.doi.org/10.1089/neu.2014.3347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4238262PMC
December 2014

Angiotensin-converting enzyme tag single nucleotide polymorphisms in patients with intracerebral hemorrhage.

Pharmacogenet Genomics 2011 Mar;21(3):136-41

Department of Neurology, Laboratory of Neurogenetics, University of Thessaly, University Hospital of Larissa, Larissa, Greece.

Objectives: 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.
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http://dx.doi.org/10.1097/FPC.0b013e328343ab15DOI Listing
March 2011

Genetic association studies in patients with traumatic brain injury.

Neurosurg Focus 2010 Jan;28(1):E9

Department of Neurology, Laboratory of Neurogenetics, University of Thessaly, University Hospital of Larissa, Larissa, Greece.

Traumatic brain injury (TBI) constitutes a major cause of mortality and disability worldwide, especially among young individuals. It is estimated that despite all the recent advances in the management of TBI, approximately half of the patients suffering head injuries still have unfavorable outcomes, which represents a substantial health care, social, and economic burden to societies. Considerable variability exists in the clinical outcome after TBI, which is only partially explained by known factors. Accumulating evidence has implicated various genetic elements in the pathophysiology of brain trauma. The extent of brain injury after TBI seems to be modulated to some degree by genetic variants. The authors' current review focuses on the up-to-date state of knowledge regarding genetic association studies in patients sustaining TBI, with particular emphasis on the mechanisms underlying the implication of genes in the pathophysiology of TBI.
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http://dx.doi.org/10.3171/2009.10.FOCUS09215DOI Listing
January 2010

Genetic association studies in osteonecrosis of the femoral head: mini review of the literature.

Skeletal Radiol 2008 Jan;37(1):1-7

Department of Neurology, Medical School, Larissa University Hospital, University of Thessaly, 22 Papakyriazi Street, Larissa 41222, Greece.

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http://dx.doi.org/10.1007/s00256-007-0395-2DOI Listing
January 2008

Paraoxonase 1 gene polymorphisms in patients with osteonecrosis of the femoral head with and without cerebral white matter lesions.

J Orthop Res 2007 Aug;25(8):1087-93

Neurogenetics Unit, Department of Neurology, School of Medicine, University of Thessaly, Larissa 41222, Greece.

Cerebral white matter lesions (WML) are present in more than 50% of patients with osteonecrosis of the femoral head (ONFH). Paraoxonase 1 (PON1) gene product is a detoxifying and pesticide metabolizing enzyme. Genetic variants of the PON1 gene have been found to influence the occurrence and progression of WML. We examined whether two PON1 polymorphisms (M55L and R192Q) are associated with ONFH and influence the occurrence of WML. We studied 104 patients with ONFH and 113 healthy age- and sex-matched subjects. We used logistic regression models to examine associations and survival analyses (Cox proportional hazards models) to examine possible influence of alleles on age at onset of ONFH. We found no association of PON1 M55L alleles and genotypes with ONFH. The distribution of PON1 Q192R alleles (p = 0.001) and genotypes (QQ vs. QR/RR) (p = 0.004) were statistically different between controls and patients. Patients with QQ genotype had six times higher risk for WML at brain MRI (adjusted OR 5.95; 95% CI 1.30-27.03; p = 0.02). In Cox models, there was a significant association of allele Q with risk for ONFH indicating a possible dose effect (HR = 1.43; 95%CI = 1.04-1.97; p for trend = 0.03). We conclude that individuals with PON1 192QQ genotype may have increased risk for ONFH and WMLeOn.
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http://dx.doi.org/10.1002/jor.20393DOI Listing
August 2007