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- Chen, Dan, et al.
(författare)
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Pooled analysis of genome-wide association studies of cervical intraepithelial neoplasia 3 (CIN3) identifies a new susceptibility locus
- 2016
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:27, s. 42216-42224
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Tidskriftsartikel (refereegranskat)abstract
- Recent genome-wide association studies (GWASs) in subjects of European descent have identified associations between cervical cancer risk and three independent loci as well as multiple classical human leukocyte antigen (HLA) alleles at 6p21.3. To search for novel loci associated with development of cervical cancer, we performed a pooled analysis of data from two GWASs by imputing over 10 million genetic variants and 424 classical HLA alleles, for 1,553 intraepithelial neoplasia 3 (CIN3), 81 cervical cancer and 4,442 controls from the Swedish population. Notable findings were validated in an independent study of 961 patients (827 with CIN3 and 123 with cervical cancer) and 1,725 controls. Our data provided increased support for previously identified loci at 6p21.3 (rs9271898, P = 1.2 x 10(-24); rs2516448, 1.1 x 10(-15); and rs3130196, 2.3 x 10(-9), respectively) and also confirmed associations with reported classical HLA alleles including HLA-B*07:02, -B*15:01, -DRB1*13:01, -DRB1*15:01, -DQA1*01:03, -DQB1*06:03 and -DQB1*06:02. In addition, we identified and subsequently replicated an independent signal at rs73730372 at 6p21.3 (odds ratio = 0.60, 95% confidence interval = 0.54-0.67, P = 3.0 x 10(-19)), which was found to be an expression quantitative trait locus (eQTL) of both HLA-DQA1 and HLA-DQB1. This is one of the strongest common genetic protective variants identified so far for CIN3. We also found HLA-C*07:02 to be associated with risk of CIN3. The present study provides new insights into pathogenesis of CIN3.
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| 2. |
- Hua, Weijie, et al.
(författare)
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Understanding the Influence of Guest-Host Interactions on the Conformation of Short Peptides in a Hydrophobic Cavity : A Computational Study
- 2011
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Ingår i: ChemPhysChem. - : Wiley. - 1439-4235 .- 1439-7641. ; 12:7, s. 1325-1333
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Tidskriftsartikel (refereegranskat)abstract
- We performed a computational investigation to understand the conformational preferences of four short peptides in a self-assembled cage based on the experimental work by Y. Hatakeyama et al. (Angew. Chem. Int. Ed. 2009, 48, 8695). For this purpose, we combined molecular dynamics simulations, Monte Carlo simulations, and quantum mechanical calculations to obtain energies and structures for several low-lying conformers of four peptides and the corresponding peptide-cage inclusion complexes. Our calculations at both B3LYP and MP2 levels show that for each peptide, the corresponding conformation within the host (as revealed by the crystal structure) does not represent the lowest-energy conformation of this peptide in vacuum. By comparing some low-lying conformers in vacuum and in the cavity (for the same peptide), we found that the cage has a significant influence on the conformational propensities of peptides. First, one carbonyl oxygen of each peptide tends to bind to one Zn (II) atom of the cage, forming a Zn-O bond. The formation of this bond leads to significant charge transfer from the cage to the peptide. Second, this Zn-O bond causes the peptide to go through some local conformational changes. For larger peptides, such as penta-and hexapeptides, our calculations also show that some of their conformers must undergo significant structural changes, due to the confinement of the host. This computational study reveals the noticeable influence of the guest-host interaction on the conformational preferences of short peptides.
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