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WP6: Validation - computational, functional and structural studies

Polymorphisms of the CD24 Gene Are Associated with Risk of Multiple Sclerosis: A Meta-Analysis

CD24 is a cell-surface protein mainly expressed in cells of the immune and central nervous system (CNS), cells that play a critical role in the development of multiple sclerosis (MS). In the current study, we investigated four polymorphisms of the CD24 gene regarding their associations with MS. To this end, univariate and multivariate meta-analysis were applied along with modifications to include data from family-trios so as to increase the robustness of the meta-analysis. We found that the polymorphism 226 C>T (Ala57Val) of the CD24 gene is associated with MS according to the recessive mode of inheritance (odds ratio = 1.75; 95% CI: 1.09, 2.81). Moreover, the 1527–1528 TG>del polymorphism is inversely associated with MS according to the dominant mode of inheritance (odds ratio = 0.57; 95% CI 0.39, 0.83). Conversely, the 1056 A>G and 1626 A>G polymorphisms were not found to be associated with MS. We conclude that the CD24 226 C>T polymorphism increases the risk of MS, while the 1527–1528 TG>del polymorphism seems to have a protective role against MS, suggesting that these two polymorphisms can be used as predictive biomarkers for MS development.

A meta-analysis of FZD3 polymorphisms and their association with schizophrenia

The aim of the present study is to investigate the potential association of FZD3 polymorphisms with schizophrenia. A systematic review and a meta-analysis were conducted comprising of nine individual studies with both population based and family based design. Totally 2 283 schizophrenic patients and 2 924 healthy individuals were involved in the analysis while six polymorphisms were examined: rs2241802, rs2323019, rs352203, rs3757884, rs880481 and rs960914. A summary-based method for pooling genetic association studies under both family-based and population-based designs was used. Odds ratios (ORs) along with their 95% confidence intervals (CIs) were computed to compare the contrast of alleles in patients and controls. Several diagnostics were performed in order to detect various forms of bias. When statistical significance was not reached, the amount of additional information required to obtain a statistical significant result was estimated. The results indicate a potentially weaker effect of FZD3 polymorphisms on schizophrenia than that originally suggested and possibly limited to Chinese populations. No relationship was identified between all examined polymorphisms and schizophrenia, except for rs352203. The rs352203 polymorphism has a protective role against schizophrenia. However this effect was mainly attributed to studies including Chinese patients. In Chinese population was also identified an elevated risk for schizophrenia of rs2323019 polymorphism. Given the different linkage disequilibrium patterns observed in Chinese, schizophrenia may be related to some other polymorphisms of FZD3 that are in stronger linkage disequilibrium to Chinese than to the other populations studied.

A meta-analysis of TNXB polymorphisms and their association with schizophrenia

The genetic etiology of schizophrenia makes necessary a better understanding of the genes that are reportedly associated with it. This study aims to examine the potential association of three polymorphisms of TNXB gene with schizophrenia through a meta-analytic approach. Four publications were used in the analysis, involving both family-based and population-based studies. The results revealed non-significant association between rs1009382, rs204887, rs204900 TNXB gene polymorphisms and schizophrenia.

Genetic Polymorphisms of ACE, eNOS and CBLN2 genes and their association with pulmonary arterial hypertension: a case-control study and a meta-analysis

Pulmonary hypertension is a rare disease characterized by progressively expanding morphological changes throughout the vasculature of the lung, leading to increased blood pressure in the lungs. These changes lead to heart failure and other medical conditions. In the absence of treatment, life expectancy is less than three years. Pulmonary hypertension can occur as hereditary, idiopathic or a complication of other diseases. The genetic etiology of the disease is still unclear, given the low penetration of dominant mutations of BMPR2 gene found only in 70% of heritable PAH and 15% of idiopathic PAH. The present work is a case-control study and meta-analysis of such studies. It is an attempt to investigate novel genetic associations of genes not involved in the BMPR2 pathway. The ACE I/D and VNTR of 27bp of NOS3 polymorphisms were selected to be investigated for genetic association with PAH because previous cases-control studies have shown association with both primary PAH and COPD-caused PAH. Additionally, the rs2217560 was also explored because it was shown to be associated with PAH in a GWAS. We found 64 I and 112 D alleles of the ACE gene in patients, while in healthy controls 74 I and 102 D alleles. In a meta-analysis of three studies (including this) the D vs I allele contrast yielded marginally non statistically significant association with OR 1,52 and confidence interval 0.95 to 2.44 indicating ACE I/D polymorphism as a candidate biomarker for PAH predisposition.

International Journal Publications

  • Georgia G. Braliou, Katerina G. Pantavou, Panagiota I. Kontou and Pantelis G. Bagos Polymorphisms of the CD24 gene are associated with risk of Multiple Sclerosis: a meta-analysis. International Journal of Molecular Sciences. 2015, 16(6): 12368-12381.
  • Katerina Pantavou, Georgia Braliou, Panagiota Kontou, Niki Dimou and Pantelis Bagos A meta-analysis of FZD3 gene polymorphisms and their association with schizophrenia. (in final stage of preparation)
  • Georgia G. Braliou, Christina Vasiliou, Maria Kampa, Argyri Gialeraki, Eleni Vrigkou, Iraklis Tsangaris, and Pantelis G. Bagos Genetic Polymorphisms of ACE, eNOS and CBLN2 genes and their association with pulmonary arterial hypertension: a case-control study and a meta-analysis. (in preparation)

Posters and oral presentations in International and National Conferences

  • Georgia Braliou, Katerina Pantavou, Panagiota Kontou, Pantelis Bagos CD24 genetic polymorphisms are associated with risk for Multiple Sclerosis development and progression: A meta-analysis, 9th Conference of Hellenic Society for Computational Biology and Bioinformatics (HSCBB), Agricultural University of Athens, Athens, Greece, 10-12 October 2014.
  • Katerina Pantavou, Georgia Braliou, Panagiota Kontou, Niki Dimou and Pantelis Bagos Polymorphisms of FZD3 gene and schizophrenia: a meta-analysis, 37th Scientific Conference of Hellenic Society of Biological Sciences, Volos, Greece, 21-23 May 2015.
  • Katerina G. Pantavou, Maria S. Syntichaki, Georgia G. Braliou, Niki L. Dimou and Pantelis G. Bagos ΤΝΧΒ genetic polymorphisms and schizophrenia: a meta-analysis, 10th Conference of Hellenic Society for Computational Biology and Bioinformatics (HSCBB), Biomedical Research Foundation Academy of Athens (BRFAA/IIBEAA), Athens, Greece, 9-11 October 2015.