Study on a novel polymorphism in the VKORC1 promoter region using bioinformatic tools and warfarin dosing data

Askari, Behnam; Khaleqsefat, Esmat; Khalafkhani, Davood; Khalaj‐Kondori, Mohammad; Khademvatan, Kamal; Soraya, Hamid

doi:10.1016/j.thromres.2017.08.012

Cited by 5 publications

(4 citation statements)

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“…When the alleles of rs7294, rs2359612, rs805894 and rs9934438 are "G", "T", "G" and "C" respectively, the effective warfarin dose required by thromboembolism patients is lower. 9,12,35,36 The FDA has specified that the use of warfarin in clinical trials should be subject to genetic testing for VKORC1. 34 Our research data made up for the lack of pharmacogenomic data among Chinese ethnic minorities, and provided negligible help for the clinical medication of five ethnic minorities in Heilongjiang Province, China.…”

Section: Discussionmentioning

confidence: 99%

Genetic Polymorphism of Drug Metabolic Gene CYPs, VKORC1, NAT2, DPYD and CHST3 of Five Ethnic Minorities in Heilongjiang Province, Northeast China

Zhang¹,

Li²,

Dong³

et al. 2021

PGPM

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Introduction: Genetic variability in genes encoding drug-metabolizing enzymes may contribute to the heterogeneity of drug responses in different populations. Extensive research in pharmacogenomics in major populations around the world provides us with a great deal of information about drug-related genetic polymorphisms. Objective: The purpose of this study was to detect the genetic variation of drug-metabolism -related genes in the five ethnic minorities Daur, Hezhen, Ewenki, Mongolian and Manchu in China, and to analyze the distribution differences among ethnic groups. Methods: We genotyped 32 SNPs of drug metabolism genes in 882 healthy Chinese volunteers from five ethnic groups. The genotype frequency and allele frequency of the five ethnic groups were calculated, and the different variants among the five ethnic groups were compared by chi-square test. Genetic parameters were analyzed using Popgene software. The genetic structure of five ethnic minorities was analyzed by principal component analysis, and compared with 26 populations. Results: We found that SNPs of genes related to drug metabolism existed diversity in different populations. Among them, rs8192766 and rs9419082 in CYP2E1 showed statistical differences between Daur and Manchu, and NAT2 rs1801280 showed statistical differences between Hezhen and Mongolian. In addition, the five populations we studied had the smallest differences with EAS populations. There was haplotype diversity in CHST3, VKORC1, CYP1A2 and CYP2E1 genes in the five ethnic minorities, and these haplotype polymorphisms were related to the use of corresponding drug doses. Cluster analysis shows that the five ethnic minorities in Heilongjiang Province are clustered together with the EAS populations. Conclusion: These results suggest that understanding the diversity of drug-related genetic markers is critical for individualized drug gene therapy programs in ethnic minorities in China as well as in populations highly mixed with these ethnic groups.

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Section: Discussionmentioning

confidence: 99%

Genetic Polymorphism of Drug Metabolic Gene CYPs, VKORC1, NAT2, DPYD and CHST3 of Five Ethnic Minorities in Heilongjiang Province, Northeast China

Zhang¹,

Li²,

Dong³

et al. 2021

PGPM

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“…[7] VKORC1 (rs9923231) was a common single-nucleotide polymorphism (SNP) in VKORC1, leading to a protein product with no enzyme activity. [8] The mutation frequency of VKORC1 (rs9923231) is about 40% in Caucasians and 10% in Africans, but affects up to near 95% in Asians. [8] Unlike VKORC1 (rs9923231), the mutation rate of CYP2C9∗3 was only 2% to 5% in Asians.…”

Section: Discussionmentioning

confidence: 99%

“…[8] The mutation frequency of VKORC1 (rs9923231) is about 40% in Caucasians and 10% in Africans, but affects up to near 95% in Asians. [8] Unlike VKORC1 (rs9923231), the mutation rate of CYP2C9∗3 was only 2% to 5% in Asians. [9] In the present case, the reduced-function allele carrier of both VKORC1 and CYP2C9 induced a relatively low dosage of warfarin.…”

Section: Discussionmentioning

confidence: 99%

Optimal nonvitamin K antagonist oral anticoagulant therapy in a warfarin-sensitive patient after left atrial appendage closure

Shen

Fang

et al. 2018

Medicine

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“…However, it is known that VKOR is associated with the ER disulphide forming pathway, 120,121 and ER transcription factors, such as XBP1, may affect the expression of VKORC1 gene. 122…”

Section: Endoplasmic Reticulum Stressmentioning

confidence: 99%

Role of vascular remodeling in atherosclerosis and aortic aneurysm

Petsophonsakul

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Study on a novel polymorphism in the VKORC1 promoter region using bioinformatic tools and warfarin dosing data

Cited by 5 publications

References 11 publications

Genetic Polymorphism of Drug Metabolic Gene CYPs, VKORC1, NAT2, DPYD and CHST3 of Five Ethnic Minorities in Heilongjiang Province, Northeast China

Genetic Polymorphism of Drug Metabolic Gene CYPs, VKORC1, NAT2, DPYD and CHST3 of Five Ethnic Minorities in Heilongjiang Province, Northeast China

Optimal nonvitamin K antagonist oral anticoagulant therapy in a warfarin-sensitive patient after left atrial appendage closure

Role of vascular remodeling in atherosclerosis and aortic aneurysm

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