Genetic factors associated with patient-specific warfarin dose in ethnic Indonesians

<p>Abstract</p> <p>Background</p> <p><it>CYP2C9 </it>and <it>VKORC1 </it>are two major genetic factors associated with inter-individual variability in warfarin dose. Additionally, genes in the warfarin metabolism pathway have also been associated with dose variance. We analyzed Single Nucleotide Polymorphisms (SNPs) in these genes to identify genetic factors that might confer warfarin sensitivity in Indonesian patients.</p> <p>Methods</p> <p>Direct sequencing method was used to identify SNPs in <it>CYP2C9, VKORC1, CYP4F2, EPHX1, PROC </it>and <it>GGCX </it>genes in warfarin-treated patients. Multiple linear regressions were performed to model the relationship warfarin daily dose requirement with genetic and non-genetic variables measured and used to develop a novel algorithm for warfarin dosing.</p> <p>Results</p> <p>From the 40 SNPs analyzed, <it>CYP2C9 </it>rs17847036 and <it>VKORC1 </it>rs9923231 showed significant association with warfarin sensitivity. In our study population, no significant correlation could be detected between <it>CYP2C9*3, CYP2C9C</it>-65 (rs9332127), <it>CYP4F2 </it>rs2108622, <it>GGCX </it>rs12714145, <it>EPHX1 </it>rs4653436 and <it>PROC </it>rs1799809 with warfarin sensitivity.</p> <p>Conclusions</p> <p><it>VKORC1 </it>rs9923231 AA and <it>CYP2C9 </it>rs17847036 GG genotypes were associated with low dosage requirements of most patients (2.05 ± 0.77 mg/day and 2.09 ± 0.70 mg/day, respectively). <it>CYP2C9 </it>and <it>VKORC1 </it>genetic variants as well as non-genetic factors such as age, body weight and body height account for 15.4% of variance in warfarin dose among our study population. Additional analysis of this combination could allow for personalized warfarin treatment in ethnic Indonesians.</p

Phases of Dense Matter in Compact Stars

Formed in the aftermath of gravitational core-collapse supernova explosions, neutron stars are unique cosmic laboratories for probing the properties of matter under extreme conditions that cannot be reproduced in terrestrial laboratories. The interior of a neutron star, endowed with the highest magnetic fields known and with densities spanning about ten orders of magnitude from the surface to the centre, is predicted to exhibit various phases of dense strongly interacting matter, whose physics is reviewed in this chapter. The outer layers of a neutron star consist of a solid nuclear crust, permeated by a neutron ocean in its densest region, possibly on top of a nuclear “pasta” mantle. The properties of these layers and of the homogeneous isospin asymmetric nuclear matter beneath constituting the outer core may still be constrained by terrestrial experiments. The inner core of highly degenerate, strongly interacting matter poses a few puzzles and questions which are reviewed here together with perspectives for their resolution. Consequences of the dense-matter phases for observables such as the neutron-star mass-radius relationship and the prospects to uncover their structure with modern observational programmes are touched upon.info:eu-repo/semantics/publishe