A warfarin-dosing model in Asians that uses single-nucleotide polymorphisms in vitamin K epoxide reductase complex and cytochrome P450 2C9

Abstract

Warfarin dose requirements in Asians can be accurately predicted by use of a combination of patient demographics and a simplified genotyping approach for single variants in CYP2C9 and VKORC1.

Accuracy assessment of pharmacogenetic algorithms for warfarin dose prediction in Chinese patients

“…Algorithms were selected based on the following criteria: the algorithms that included nongenetic or genetic variables not available in our study, and included only a minority of clinical variables, and were based on relatively small clinical populations were excluded; algorithms that were derived from Asian with the consideration of race of each algorithm made up of at least 15% Asians in original populations, and algorithms validated best in Asians were included. This process identified eight algorithms [12][13][14][15][16][17][18][19]. The characteristics and equations of selected algorithms are listed in Supporting Information Tables II and III. Collection of subjects and clinical data.…”

“…For Chinese patients, the optimal INR might be set at 1.6-2.5, in contrast to the 2.0-3.0 range set in most studies [11]. Several pharmacogenetic algorithms, based on a variety of clinical and genetic parameters including the CYP2C9 and VKORC1 genes as variables, have been proposed based on Asian populations [12][13][14]. Comparison of warfarin dose predictive pharmacogenetic algorithms can be performed to determine the optimal algorithm for our Chinese population.…”

“…In the interest of determining an accurate predictive pharmacogenetic algorithm to promote rational treatment, especially for Chinese outliers, we attempted to assess the predictive ability of published warfarin pharmacogenetic dosing algorithms in Mainland Han Chinese [12][13][14][15][16][17][18][19].…”

“…Studies have shown the efficacy of TCD in identifying stenotic intracranial vessels in the circle of Willis and thus asymptomatic children who are at an increased risk of stroke [1,12]. The narrowing of intracranial vessels in SCD results from fibrous proliferation of the intima and in some cases, thrombi formation.…”

“…The lesions apparently progress for months or years before cerebral symptoms develop and so there is an opportunity to detect vascular narrowing before cerebral lesions develop. Flow velocities of 200 cm/sec in the middle cerebral or the internal carotid arteries has been reported to be associated with 40% risk of developing a stroke while flow velocities of <170 cm/sec and 170-199 cm/sec are associated with a stroke-risk of 2% and 7%, respectively [12]. Low arterial oxygen saturation <95% and a history of 3 febrile episodes in the preceding year were reported to predict a high CBF in a cohort of Kenyan children with SCD [13].…”