Kallirhoe Kalinderi

Complete screening for glucocerebrosidase mutations in Parkinson disease patients from Greece

Mutations in beta-glucocerebrosidase gene (GBA) have been implicated in Parkinson disease (PD). A Greek cohort of 172 PD patients and 132 control individuals were screened for GBA mutations by complete sequencing of the genes exons. Four mutations previously associated with Gaucher disease and/or Parkinsons disease (L445P, D409H, E326K, H255Q) were detected, as well as five newly identified variants (R329H, L268L, S271G, T428K, V460L), providing for the first time data regarding the frequency of GBA mutations among PD patients and controls, in the Greek population. H255Q was the most common GBA mutation among Greek PD patients (4/172). V460L was only found in control individuals (2/132). Overall, GBA mutations were significantly overrepresented in a subgroup of early onset PD patients, compared to controls (P = 0.019, OR = 4.2; 95%CI = 1.28 -- 13.82), suggesting that GBA mutations may modify age of onset for PD.

The genetic background of Parkinson's disease: current progress and future prospects.

Almost two decades of genetic research in Parkinsons disease (PD) have remarkably increased our knowledge regarding the genetic basis of PD with numerous genes and genetic loci having been found to cause familial PD or affect the risk for PD. Approximately 5–10% of PD patients have monogenic forms of the disease, exhibiting a classical Mendelian type of inheritance, however, the majority PD cases are sporadic, probably caused by a combination of genetic and environmental risk factors. Nowadays, six genes, alpha synuclein, LRRK2, VPS35, Parkin, PINK1 and DJ‐1, have definitely been associated with an autosomal dominant or recessive PD mode of inheritance. The advent of genome‐wide association studies (GWAS) and the implementation of new technologies, like next generation sequencing (NGS) and exome sequencing has undoubtedly greatly aided the identification on novel risk variants for sporadic PD. In this review, we will summarize the current progress and future prospects in the field of PD genetics.

Elevated Serum Levels of Interleukin-6, Interleukin-1β and Human Chorionic Gonadotropin in Pre-eclampsia

Citation Kalinderis M, Papanikolaou A, Kalinderi K, Ioannidou E, Giannoulis C, Karagiannis V, Tarlatzis BC. Elevated serum levels of interleukin‐6, interleukin‐1β and human chorionic gonadotropin in pre‐eclampsia. Am J Reprod Immunol 2011; 66: 468–475

Pharmacological treatment and the prospect of pharmacogenetics in Parkinson's disease.

Parkinson disease (PD) is a progressive movement disorder marked by tremor, rigidity, bradykinesia and postural instability. Levodopa (l‐dopa), usually combined with a peripheral dopa decarboxylase inhibitor, has been proved to provide the best symptomatic benefit for PD. However, its long‐term efficacy is limited because of motor complications and drug‐induced dyskinesia. Dopamine agonists, catechol‐O‐methyltransferase inhibitors and monoamine oxidase‐B inhibitors are anti‐parkinsonian (anti‐PD) drugs that have been found to further improve the potency of l‐dopa and prevent the onset of motor complications. However, as PD is a progressive disorder, all the drugs used for its therapy, manifest reduced efficacy and adverse effects with time. Research on the field of pharmacogenetics has pointed out that the genetic variability of each individual determines to a large extent the inter‐individual variability in response to anti‐PD drugs. Clinicogenetic trials show that drug efficacy or toxicity or susceptibility to side effects are features governed by genetic principles. This article is a review of the present pharmacological treatment of PD and current pharmacogenetic data for PD.

Association of the Tau haplotype with Parkinson's disease in the Greek population.

We compared the distribution of the Tau H1 haplotype and related subhaplotypes in a group of clinically diagnosed Parkinsons disease patients (n = 133) and in control individuals (n = 113) from northern Greece. We were able to detect a statistically significant overrepresentation of the H1H1 genotype in our patient group (OR for H1H1 vs. H1H2 and H2H2: 1.73; 95% CI: 1.03–2.90; P = 0.037). The H1 subhaplotype significantly associated with the disease in our population was different from the one previously reported for a Norwegian population, suggesting that the nature of the association of Tau with Parkinsons disease is influenced by ethnic variation.

GSK3β polymorphisms, MAPT H1 haplotype and Parkinson's disease in a Greek cohort

To determine whether polymorphisms in the microtubule-associated protein tau (MAPT) and/or glycogen synthase kinase-3β (GSK3β) genes underpin susceptibility to Parkinsons disease (PD), we conducted a case-control association study in a Greek cohort of 196 PD cases and 163 healthy controls. In our study, the MAPT H1 haplotype was found to be significantly associated with PD, no association was detected between the intronic rs6438552 (-157 T/C) GSK3β polymorphism and PD, whereas the C/C genotype of the promoter rs334558 (-50 T/C) GSK3β polymorphism was found to exert a protective role. The C/C genotype of the rs334558 GSK3β polymorphism was also found to have an additional protective role in our MAPT H1/H1 PD subgroup. Haplotype analysis revealed that, the T-T haplotype of both GSK3β polymorphisms was over-represented in PD patients compared to controls, and this association was independent of MAPT H1 haplotype.

Association of brain-derived neurotrophic factor (BDNF) and elongator protein complex 4 (ELP4) polymorphisms with benign epilepsy with centrotemporal spikes in a Greek population.

PURPOSE Benign epilepsy with centrotemporal spikes (BECTS) is considered to be the most common childhood epileptic syndrome. Different mutations in genes that control the excitability of neurons have been described. Recent reports on the involvement of the BDNF and ELP4 genes in cell motility, migration, and adhesion raise the possibility that these genes are involved in pathogenesis of BECTS. MATERIALS AND METHODS We conducted a case-control association study on 60 patients with BECTS and 60 control participants to assess the influence of the BDNF and ELP4 polymorphisms on BECTS. The polymorphisms were detected with a PCR-RFLP method. Moreover, we explored the possible association of these polymorphisms with clinical and electroencephalographic parameters of patients with BECTS. RESULTS Our results show no difference in BDNF and ELP4 genotype frequencies between patients and controls. Haplotype analysis also revealed no statistical difference. CONCLUSION The role of BDNF and ELP4 polymorphisms remains controversial.

Association of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism with Parkinson's disease in a Greek population.

Brain-derived neurotrophic factor (BDNF) enhances survival of dopaminergic neurons in the substantia nigra, whereas in patients with Parkinsons disease (PD), the expression of BDNF mRNA is decreased, thus making BDNF a candidate gene for PD susceptibility. The association between BDNF Val66Met polymorphism and PD has been evaluated in several studies with controversial results. Thus, we determined the distribution of BDNF Val66Met polymorphism in 184 Greek patients with sporadic PD and 113 control participants using polymerase chain reaction-restriction fragment length polymorphism, and explored the association of the polymorphism with certain clinical parameters of the disease. Our results do not support a major role for the BDNF Val66Met polymorphism in PD in the Greek population.

From 1997 to 2007: A decade journey through the H1 haplotype on 17q21 chromosome

The H1 haplotype was first identified 10 years ago. Initially, a dinucleotide polymorphism was detected in the tau (MAPT) gene and was subsequently found to be in linkage disequilibrium (LD) with other polymorphisms, forming the MAPT H1 haplotype, a risk factor for many neurological diseases, considered as tauopathies. Genetic and histopathologic data are in agreement that MAPT and its encoded protein have a pivotal role in the normal function of neurons. Currently, the H1 haplotype extends beyond the outer edges of MAPT encompassing multiple genes on chromosome 17 and thus increasing the number of candidate genes implicated in the pathogenesis of tauopathies. This review highlights the milestones and basic events in the journey towards uncovering the significance of the H1 haplotype.

The G2019S LRRK2 mutation is uncommon amongst Greek patients with sporadic Parkinson's disease.

Parkinsons disease (PD) is the second most common neurodegenerative disorder affecting approximately 2% of the population >60 years of age. Although, the etiology of PD is still unknown, the genetic background of the disease has been documented. Recently, a mutation in the LRRK2 gene, G2019S, was associated with 3–41% and 1–2% of familial and sporadic PD, respectively suggesting a pivotal role of LRRK2 in PD. In this report, we examine the association of the G2019S mutation with sporadic late‐onset PD, in an independent cohort of Greek patients and controls.