| 1. |
- Perera, Minoli A., et al.
(författare)
-
Genetic variants associated with warfarin dose in African-American individuals : a genome-wide association study
- 2013
-
Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 382:9894, s. 790-796
-
Tidskriftsartikel (refereegranskat)abstract
- Background VKORC1 and CYP2C9 are important contributors to warfarin dose variability, but explain less variability for individuals of African descent than for those of European or Asian descent. We aimed to identify additional variants contributing to warfarin dose requirements in African Americans. Methods We did a genome-wide association study of discovery and replication cohorts. Samples from African-American adults (aged >= 18 years) who were taking a stable maintenance dose of warfarin were obtained at International Warfarin Pharmacogenetics Consortium (IWPC) sites and the University of Alabama at Birmingham (Birmingham, AL, USA). Patients enrolled at IWPC sites but who were not used for discovery made up the independent replication cohort. All participants were genotyped. We did a stepwise conditional analysis, conditioning first for VKORC1 -1639G -> A, followed by the composite genotype of CYP2C9*2 and CYP2C9*3. We prespecified a genome-wide significance threshold of p<5x10(-8) in the discovery cohort and p<0.0038 in the replication cohort. Findings The discovery cohort contained 533 participants and the replication cohort 432 participants. After the prespecified conditioning in the discovery cohort, we identified an association between a novel single nucleotide polymorphism in the CYP2C cluster on chromosome 10 (rs12777823) and warfarin dose requirement that reached genome-wide significance (p=1.51x10(-8)). This association was confirmed in the replication cohort (p=5.04x10(-5)); analysis of the two cohorts together produced a p value of 4.5x10(-12). Individuals heterozygous for the rs12777823 A allele need a dose reduction of 6.92 mg/week and those homozygous 9.34 mg/week. Regression analysis showed that the inclusion of rs12777823 significantly improves warfarin dose variability explained by the IWPC dosing algorithm (21% relative improvement). Interpretation A novel CYP2C single nucleotide polymorphism exerts a clinically relevant effect on warfarin dose in African Americans, independent of CYP2C9*2 and CYP2C9*3. Incorporation of this variant into pharmacogenetic dosing algorithms could improve warfarin dose prediction in this population.
|
|
| 2. |
|
|
| 3. |
- Pluzhnikov, V. B., et al.
(författare)
-
Pressure effect on the Fermi surface and electronic structure of LuGa3 and TmGa3
- 2005
-
Ingår i: LOW TEMPERATURE PHYSICS. - : AIP Publishing. - 1063-777X .- 1090-6517. ; 31:3-4, s. 313-
-
Tidskriftsartikel (refereegranskat)abstract
- The Fermi surfaces and cyclotron masses of LuGa3 and TmGa3 compounds are Studied by means of the de Haas-van Alphen effect, technique under pressure. Highly anisotropic pressure dependences of the de Haas-van Alphen frequencies and cyclotron masses are observed ill both compounds. Concurrently, ab initio calculations of the volume-dependent band structures are been carried out for these compounds, including the ferromagnetic-configuration phase of TmGa3, by employing a relativistic version of the full-potential linear muffin-tin orbital method within the local spin-density approximation. The experimental data are analyzed oil the basis of the calculated volume-dependent hand structures and compared with the corresponding pressure effects in the isostructural compound ErGa3.
|
|
| 4. |
- Pluzhnikov, VB, et al.
(författare)
-
Effect of pressure on the Fermi surface and electronic structure of ErGa3
- 1999
-
Ingår i: LOW TEMPERATURE PHYSICS. - : AMER INST PHYSICS. - 1063-777X. ; 25:8-9, s. 670-676
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The Fermi surface and cyclotron masses of the ErGa3 compound are studied by means of the de Haas-van Alphen technique under pressure. Concurrently, the electronic structure is calculated ab initio for the ferromagnetic phase of ErGa3. The experimental dat
|
|
