Genetic and Nongenetic Determinants of Variable Warfarin Dose Requirements: A Report from North India.

IF 1.3 4区医学 Q4 GENETICS & HEREDITY

Public Health Genomics Pub Date : 2021-10-21 DOI:10.1159/000519462

Navjot Kaur, Avaneesh Pandey, Nusrat Shafiq, Ankur Gupta, Reena Das, Harkant Singh, Jasmina Ahluwalia, Samir Malhotra

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引用次数: 0

Abstract

Introduction: Warfarin is widely used and will continue to be prescribed especially in developing countries due to its low cost. Given the huge patient load requiring anticoagulation, there is a need to develop strategies to optimize warfarin therapy for ensuring safe and effective anticoagulation. In the present work, we aimed at elucidating the association of genetic and nongenetic variables with warfarin dose requirement in patients attending the cardiovascular clinic in a tertiary care center of North India.

Methods: This was a prospective study conducted over 1 year. Patient demographic and clinical details were captured in customized case record forms. Genotyping was done using the polymerase chain reaction-restriction fragment length polymorphism method. Pharmacogenetic influence of CYP2C9 (rs1799853 and rs1057910) and VKORC1 (rs9923231) variant alleles was studied. The association of genetic and nongenetic factors with warfarin dose was quantified using a stepwise multivariate linear regression model.

Results: Two hundred and forty patients were screened. Data from 82 eligible patients were used for quantifying the association of genetic and nongenetic factors with warfarin dose. A descriptive model based on CYP2C9*3 (rs1057910) and VKORC1 (rs9923231) variant alleles and BMI was developed. The model explains nearly half of the interindividual variation in warfarin dose requirement.

Conclusion: The model explains nearly half of the interindividual variation in warfarin dose in patients with atrial fibrillation and or requiring valve replacement.

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华法林剂量需求变化的遗传和非遗传决定因素：北印度报告

导言：华法林因其价格低廉而被广泛使用，并将继续被处方，尤其是在发展中国家。鉴于需要抗凝治疗的患者数量巨大，有必要制定优化华法林治疗的策略，以确保安全有效的抗凝治疗。本研究旨在阐明北印度一家三级医疗中心心血管门诊就诊患者的遗传和非遗传变量与华法林剂量需求的关系：这是一项为期一年的前瞻性研究。患者的人口统计学和临床详情均记录在定制的病例记录表中。采用聚合酶链式反应-限制性片段长度多态性方法进行基因分型。研究了 CYP2C9（rs1799853 和 rs1057910）和 VKORC1（rs9923231）变异等位基因的药物遗传学影响。采用逐步多变量线性回归模型量化了遗传因素和非遗传因素与华法林剂量的关系：筛查了 240 名患者。结果：共筛选出 240 名患者，其中 82 名符合条件的患者的数据被用于量化遗传因素和非遗传因素与华法林剂量的关系。建立了一个基于 CYP2C9*3 (rs1057910) 和 VKORC1 (rs9923231) 变异等位基因和体重指数的描述性模型。该模型可解释华法林剂量需求近一半的个体间差异：该模型可解释心房颤动和需要置换瓣膜的患者华法林剂量近一半的个体间差异。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Public Health Genomics 医学-公共卫生、环境卫生与职业卫生

CiteScore

2.90

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： ''Public Health Genomics'' is the leading international journal focusing on the timely translation of genome-based knowledge and technologies into public health, health policies, and healthcare as a whole. This peer-reviewed journal is a bimonthly forum featuring original papers, reviews, short communications, and policy statements. It is supplemented by topic-specific issues providing a comprehensive, holistic and ''all-inclusive'' picture of the chosen subject. Multidisciplinary in scope, it combines theoretical and empirical work from a range of disciplines, notably public health, molecular and medical sciences, the humanities and social sciences. In so doing, it also takes into account rapid scientific advances from fields such as systems biology, microbiomics, epigenomics or information and communication technologies as well as the hight potential of ''big data'' for public health.