AUTHOR=Wang Dongxu , Wu Hualan , Dong Min , Zhang Qing , Zhao Anxu , Zhao Xinlong , Chong Jia , Du Minghui , Wang Yan , Shi Haifeng , Wang Shuanghu , Wang Fang , Cai Jianping , Yang Jiefu , Dai Dapeng , Chen Hao 

TITLE=Clinical significance of the series of CYP2C9*non3 variants, an unignorable predictor of warfarin sensitivity in Chinese population

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.1052521

DOI=10.3389/fcvm.2022.1052521

ISSN=2297-055X

ABSTRACT=<sec><title>Backgrounds</title><p>Gene polymorphisms are critical for variations in warfarin dose. To date, more than 70 <italic>CYP2C9</italic> alleles have been identified. This study was designed to clarify the clinical significance of <italic>CYP2C9*non-3</italic> variants to warfarin sensitivity in Chinese Han patients.</p></sec><sec><title>Methods</title><p>The entire <italic>CYP2C9</italic> gene region was sequenced in 1,993 individuals, and clinical data and <italic>VKORC1</italic> genotypes were collected from 986 patients with atrial fibrillation treated with warfarin. The SKAT-O method was used to analyze the effects of <italic>CYP2C9*non-3</italic> variants on warfarin sensitivity.</p></sec><sec><title>Results</title><p>A total of 20 <italic>CYP2C9</italic> variants were identified, of which four were novel. Carriers with <italic>CYP2C9*non-3</italic> variants may have lower warfarin dose requirements, and similar to <italic>CYP2C9*3, CYP2C9*non-3</italic> variants are clearly relevant to warfarin-sensitive and highly sensitive responders.</p></sec><sec><title>Conclusion</title><p>Our results showed that, besides <italic>CYP2C9*3</italic>, the series of <italic>CYP2C9*non-3</italic> variants is an unignorable predictor for warfarin sensitivity in Chinese population. From a safety consideration, people carried such variants may need a preferred choice of NOACs when they started anticoagulation therapy.</p></sec>