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- Claussnitzer, Melina, et al.
(författare)
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Leveraging cross-species transcription factor binding site patterns: from diabetes risk Loci to disease mechanisms.
- 2014
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Ingår i: Cell. - : Elsevier BV. - 1097-4172 .- 0092-8674. ; 156:1-2, s. 343-358
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have revealed numerous risk loci associated with diverse diseases. However, identification of disease-causing variants within association loci remains a major challenge. Divergence in gene expression due to cis-regulatory variants in noncoding regions is central to disease susceptibility. We show that integrative computational analysis of phylogenetic conservation with a complexity assessment of co-occurring transcription factor binding sites (TFBS) can identify cis-regulatory variants and elucidate their mechanistic role in disease. Analysis of established type 2 diabetes risk loci revealed a striking clustering of distinct homeobox TFBS. We identified the PRRX1 homeobox factor as a repressor of PPARG2 expression in adipose cells and demonstrate its adverse effect on lipid metabolism and systemic insulin sensitivity, dependent on the rs4684847 risk allele that triggers PRRX1 binding. Thus, cross-species conservation analysis at the level of co-occurring TFBS provides a valuable contribution to the translation of genetic association signals to disease-related molecular mechanisms.
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| 2. |
- Hansson, Elisabeth K, 1954, et al.
(författare)
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Person-centred care for patients with chronic heart failure - a cost-utility analysis
- 2016
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Ingår i: European Journal of Cardiovascular Nursing. - : Oxford University Press (OUP). - 1474-5151 .- 1873-1953. ; 15:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Costs of care for patients with chronic heart failure have been estimated at between 1% and 2% of the total health care expenditure in Europe and North America. Two-thirds are for inpatient care. Person-centred care (PCC) asserts that patients are persons and should not be reduced to their diseases alone. Aims: The aim of this study was to estimate the cost–utility of PCC when compared with conventional care in patients hospitalized for worsening chronic heart failure. Methods and results: Data for the cost–utility analysis were collected alongside a prospective clinical intervention study with a controlled before and after design from 2008 to 2010. Patient-specific resources used and preference-based health status data were collected at an individual level. Only 63% received PCC as intended illustrating the difficulties of introducing new methods in established organizations. The group intended to have PCC yielded higher costs in comparison with the conventional care group. The incremental cost was estimated as €98. The costs for those who actually received PCC, per protocol (PP) (63%) were significantly (p=0.026) lower than for those in the conventional care group, with an incremental cost-saving of €863. For the first three months, patients in the conventional care group showed decreasing health-related quality of life, with a corresponding improvement in the PCC(PP) group. Conclusion: It must be emphasized, however, that these positive effects, both cheaper and somewhat better, were obtained only among those receiving the PCC intervention in its intended form, PCC(PP).
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