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

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

doi:10.3389/fcvm.2022.1052521

Clinical significance of the series of CYP2C9non3* variants, an unignorable predictor of warfarin sensitivity in Chinese population

Front Cardiovasc Med. 2022 Nov 24:9:1052521. doi: 10.3389/fcvm.2022.1052521. eCollection 2022.

Authors

Dongxu Wang^{1

2}, Hualan Wu¹, Min Dong¹, Qing Zhang¹, Anxu Zhao¹, Xinlong Zhao¹, Jia Chong¹, Minghui Du¹, Yan Wang¹, Haifeng Shi¹, Shuanghu Wang³, Fang Wang¹, Jianping Cai⁴, Jiefu Yang¹, Dapeng Dai⁴, Hao Chen¹

Affiliations

¹ Department of Cardiology, National Center of Gerontology, Beijing Hospital, Beijing, China.
² Arrhythmia Center, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing, China.
³ Laboratory of Clinical Pharmacy, The People's Hospital of Lishui, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui, China.
⁴ The Key Laboratory of Geriatrics, National Centre of Gerontology, Beijing Hospital, Beijing Institute of Geriatrics, Beijing, China.

Abstract

Backgrounds: Gene polymorphisms are critical for variations in warfarin dose. To date, more than 70 CYP2C9 alleles have been identified. This study was designed to clarify the clinical significance of CYP2C9*non-3 variants to warfarin sensitivity in Chinese Han patients.

Methods: The entire CYP2C9 gene region was sequenced in 1,993 individuals, and clinical data and VKORC1 genotypes were collected from 986 patients with atrial fibrillation treated with warfarin. The SKAT-O method was used to analyze the effects of CYP2C9*non-3 variants on warfarin sensitivity.

Results: A total of 20 CYP2C9 variants were identified, of which four were novel. Carriers with CYP2C9*non-3 variants may have lower warfarin dose requirements, and similar to CYP2C9*3, CYP2C9*non-3 variants are clearly relevant to warfarin-sensitive and highly sensitive responders.

Conclusion: Our results showed that, besides CYP2C9*3, the series of CYP2C9*non-3 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.

Keywords: CYP2C9; allele; anticoagulation; gene polymorphism; warfarin.