| 1. |
- Beecham, Ashley H, et al.
(författare)
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Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
- 2013
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
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Tidskriftsartikel (refereegranskat)abstract
- Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
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| 3. |
- Grauman, Åsa, 1982-, et al.
(författare)
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Personalizing precision medicine : Patients with AML perceptions about treatment decisions
- 2023
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Ingår i: Patient Education and Counseling. - : Elsevier BV. - 0738-3991 .- 1873-5134. ; 115
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Tidskriftsartikel (refereegranskat)abstract
- Background: This study aims to explore patients' with acute myeloid leukemia perceptions about precision medicine and their preferences for involvement in this new area of shared decision-making.Methods: Individual semi-structured interviews were conducted in Finland, Italy and Germany (n = 16). The study population included patients aged 24-79 years. Interviews were analyzed with thematic content analysis.Results: Patient's perceived lack of knowledge as a barrier for their involvement in decision-making. Treatment decisions were often made rapidly based on the patient's intuition and trust for the physician rather than on information, in situations that decrease the patient's decision capacity. The patients emphasized that they are in a desperate situation that makes them willing to accept treatment with low probabilities of being cured.Conclusions: The study raised important issues regarding patients' understanding of precision medicine and challenges concerning how to involve patients in medical decision-making. Although technical advances were viewed positively, the role of the physician as an expert and person-of-trust cannot be replaced.Practice implications: Regardless of patients' preferences for involvement in decision-making, information plays a crucial role for patients' perceived involvement in their care. The concepts related to precision medicine are complex and will imply challenges to patient education.
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| 4. |
- Martinelli, Silvia, et al.
(författare)
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ANGPT2 promoter methylation is strongly associated with gene expression and prognosis in chronic lymphocytic leukemia
- 2013
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Ingår i: Epigenetics. - : Informa UK Limited. - 1559-2294 .- 1559-2308. ; 8:7, s. 720-729
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Tidskriftsartikel (refereegranskat)abstract
- Increasing evidence suggests a key role for angiopoietin-2 (ANGPT2) in influencing the aggressiveness of chronic lymphocytic leukemia (CLL). In the presence of vascular endothelial growth factor (VEGF), ANGPT2 causes vessel destabilization leading to neoangiogenesis. Accordingly, high expression levels of ANGPT2 and high degree of angiogenesis have consistently been associated with poor prognosis in CLL; however, the molecular mechanisms behind the variability in ANGPT2 expression are still to be discovered. Here, for the first time, we investigated the DNA methylation status of the ANGPT2 promoter in a large CLL cohort (n = 88) using pyrosequencing and correlated methylation data with ANGPT2 expression levels, prognostic factors and outcome. Importantly, methylation levels of the ANGPT2 gene correlated inversely with its mRNA expression levels (p < 0.001). Moreover, low ANGPT2 methylation status was highly associated with adverse prognostic markers, shorter time to first treatment and overall survival. Finally, treatment with methyl inhibitors induced re-expression of ANGPT2 in two B-cell lymphoma cell lines, underscoring the importance of DNA methylation in regulating transcriptional silencing of this gene. In conclusion, we believe that the known variability in ANGPT2 expression among CLL patients could be explained by differential promoter DNA methylation and that low methylation levels of the ANGPT2 promoter have an adverse prognostic impact in CLL.
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| 5. |
- Piciocchi, Cinzia, et al.
(författare)
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Legal issues in governing genetic biobanks : the Italian framework as a case study for the implications for citizen's health through public-private initiatives.
- 2018
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Ingår i: Journal of Community Genetics. - : Springer Science and Business Media LLC. - 1868-310X .- 1868-6001. ; 9:2, s. 177-190
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Tidskriftsartikel (refereegranskat)abstract
- This paper outlines some of the challenges faced by regulation of genetic biobanking, using case studies coming from the Italian legal system. The governance of genetic resources in the context of genetic biobanks in Italy is discussed, as an example of the stratification of different inputs and rules: EU law, national law, orders made by authorities and soft law, which need to be integrated with ethical principles, technological strategies and solutions. After providing an overview of the Italian legal regulation of genetic data processing, it considers the fate of genetic material and IP rights in the event of a biobank's insolvency. To this end, it analyses two case studies: a controversial bankruptcy case which occurred in Sardinia, one of the first examples of private and public partnership biobanks. Another case study considered is the Chris project: an example of partnership between a research institute in Bolzano and the South Tyrolean Health System. Both cases seem to point in the same direction, suggesting expediency of promoting and improving public-private partnerships to manage biological tissues and biotrust to conciliate patent law and public interest.
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