Impact of a variable number tandem repeat in the CYP2C9 promoter on warfarin sensitivity and responsiveness in Jordanians with cardiovascular disease
Laith N AL-Eitan,1,2 Ayah Y Almasri,1 Sahar O Al-Habahbeh1 1Department of Applied Biological Sciences, Jordan University of Science and Technology, Irbid 22110, Jordan; 2Department of Biotechnology and Genetic Engineering, Jordan University of Science and Technology, Irbid 22110, Jordan Purpose: The...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2019-03-01
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| Series: | Pharmacogenomics and Personalized Medicine |
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| Online Access: | https://www.dovepress.com/impact-of-a-variable-number-tandem-repeat-in-the-cyp2c9-promoter-on-wa-peer-reviewed-article-PGPM |
| _version_ | 1819090777337233408 |
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| author | AL-Eitan LN Almasri AY Al-Habahbeh SO |
| author_facet | AL-Eitan LN Almasri AY Al-Habahbeh SO |
| author_sort | AL-Eitan LN |
| collection | DOAJ |
| description | Laith N AL-Eitan,1,2 Ayah Y Almasri,1 Sahar O Al-Habahbeh1 1Department of Applied Biological Sciences, Jordan University of Science and Technology, Irbid 22110, Jordan; 2Department of Biotechnology and Genetic Engineering, Jordan University of Science and Technology, Irbid 22110, Jordan Purpose: The purpose of this study was to investigate the influence of CYP/CYP450 2C9 (CYP2C9) promoter variable number tandem repeat (p-VNTR) polymorphism on susceptibility to cardiovascular disease and on warfarin sensitivity and responsiveness, in Jordanians with cardiovascular disease during initiation and stabilization phases of therapy. Patients and methods: A total of 211 cardiovascular patients who were being treated with warfarin anticoagulants and 205 healthy individuals were enrolled in this study. PCR-based methods were performed to analyze the effects of CYP2C9 p-VNTR polymorphism on warfarin metabolism. The p-VNTR polymorphism was composed of tandem repeat motifs sorted into three alleles based on the length and structure: short (p-VNTR-S), middle (p-VNTR-M), and long (p-VNTR-L). Results: We found that the genotypic and allelic frequencies differ significantly between patients and healthy individuals; therefore, our results suggest that this polymorphism is associated with cardiovascular disease in the Jordanian population. Moreover, during the initiation phase of therapy, 20% of warfarin-sensitive patients were homozygous for a short allele (p-VNTR-S), and 12.2% were heterozygous for this allele (p-VNTR-M/p-VNTR-S). During the stabilization phase, no significant differences were found between these groups and their genotypic frequencies. Additionally, we did not confirm any relationship between the CYP2C9 p-VNTR polymorphism and warfarin response during either the initiation or the stabilization phases of therapy. Conclusion: Our data show a significant difference between the CYP2C9 p-VNTR polymorphism and risk of cardiovascular disease, in addition to significant association between this polymorphism and sensitivity to warfarin at the initiation phase of therapy in a Jordanian population. However, there is no correlation between this polymorphism and warfarin response, international normalized ratio (INR) values, or required warfarin dose to achieve a target INR either at the initiation or stabilization phases of therapy. To further corroborate our results, additional studies are required with a larger number of samples and different ethnic groups. Keywords: warfarin, CYP2C9 promoter variable tandem repeat, polymorphism, cardiovascular disorder, oral anticoagulant, INR, warfarin dosage |
| first_indexed | 2024-12-21T22:29:13Z |
| format | Article |
| id | doaj.art-ab8651bd5db54929afed267c2a2b23e6 |
| institution | Directory Open Access Journal |
| issn | 1178-7066 |
| language | English |
| last_indexed | 2024-12-21T22:29:13Z |
| publishDate | 2019-03-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Pharmacogenomics and Personalized Medicine |
| spelling | doaj.art-ab8651bd5db54929afed267c2a2b23e62022-12-21T18:48:08ZengDove Medical PressPharmacogenomics and Personalized Medicine1178-70662019-03-01Volume 12152244693Impact of a variable number tandem repeat in the CYP2C9 promoter on warfarin sensitivity and responsiveness in Jordanians with cardiovascular diseaseAL-Eitan LNAlmasri AYAl-Habahbeh SOLaith N AL-Eitan,1,2 Ayah Y Almasri,1 Sahar O Al-Habahbeh1 1Department of Applied Biological Sciences, Jordan University of Science and Technology, Irbid 22110, Jordan; 2Department of Biotechnology and Genetic Engineering, Jordan University of Science and Technology, Irbid 22110, Jordan Purpose: The purpose of this study was to investigate the influence of CYP/CYP450 2C9 (CYP2C9) promoter variable number tandem repeat (p-VNTR) polymorphism on susceptibility to cardiovascular disease and on warfarin sensitivity and responsiveness, in Jordanians with cardiovascular disease during initiation and stabilization phases of therapy. Patients and methods: A total of 211 cardiovascular patients who were being treated with warfarin anticoagulants and 205 healthy individuals were enrolled in this study. PCR-based methods were performed to analyze the effects of CYP2C9 p-VNTR polymorphism on warfarin metabolism. The p-VNTR polymorphism was composed of tandem repeat motifs sorted into three alleles based on the length and structure: short (p-VNTR-S), middle (p-VNTR-M), and long (p-VNTR-L). Results: We found that the genotypic and allelic frequencies differ significantly between patients and healthy individuals; therefore, our results suggest that this polymorphism is associated with cardiovascular disease in the Jordanian population. Moreover, during the initiation phase of therapy, 20% of warfarin-sensitive patients were homozygous for a short allele (p-VNTR-S), and 12.2% were heterozygous for this allele (p-VNTR-M/p-VNTR-S). During the stabilization phase, no significant differences were found between these groups and their genotypic frequencies. Additionally, we did not confirm any relationship between the CYP2C9 p-VNTR polymorphism and warfarin response during either the initiation or the stabilization phases of therapy. Conclusion: Our data show a significant difference between the CYP2C9 p-VNTR polymorphism and risk of cardiovascular disease, in addition to significant association between this polymorphism and sensitivity to warfarin at the initiation phase of therapy in a Jordanian population. However, there is no correlation between this polymorphism and warfarin response, international normalized ratio (INR) values, or required warfarin dose to achieve a target INR either at the initiation or stabilization phases of therapy. To further corroborate our results, additional studies are required with a larger number of samples and different ethnic groups. Keywords: warfarin, CYP2C9 promoter variable tandem repeat, polymorphism, cardiovascular disorder, oral anticoagulant, INR, warfarin dosagehttps://www.dovepress.com/impact-of-a-variable-number-tandem-repeat-in-the-cyp2c9-promoter-on-wa-peer-reviewed-article-PGPMWarfarinCYP2C9 Promoter variable tandem repeatpolymorphismcardiovascular disorder |
| spellingShingle | AL-Eitan LN Almasri AY Al-Habahbeh SO Impact of a variable number tandem repeat in the CYP2C9 promoter on warfarin sensitivity and responsiveness in Jordanians with cardiovascular disease Pharmacogenomics and Personalized Medicine Warfarin CYP2C9 Promoter variable tandem repeat polymorphism cardiovascular disorder |
| title | Impact of a variable number tandem repeat in the CYP2C9 promoter on warfarin sensitivity and responsiveness in Jordanians with cardiovascular disease |
| title_full | Impact of a variable number tandem repeat in the CYP2C9 promoter on warfarin sensitivity and responsiveness in Jordanians with cardiovascular disease |
| title_fullStr | Impact of a variable number tandem repeat in the CYP2C9 promoter on warfarin sensitivity and responsiveness in Jordanians with cardiovascular disease |
| title_full_unstemmed | Impact of a variable number tandem repeat in the CYP2C9 promoter on warfarin sensitivity and responsiveness in Jordanians with cardiovascular disease |
| title_short | Impact of a variable number tandem repeat in the CYP2C9 promoter on warfarin sensitivity and responsiveness in Jordanians with cardiovascular disease |
| title_sort | impact of a variable number tandem repeat in the cyp2c9 promoter on warfarin sensitivity and responsiveness in jordanians with cardiovascular disease |
| topic | Warfarin CYP2C9 Promoter variable tandem repeat polymorphism cardiovascular disorder |
| url | https://www.dovepress.com/impact-of-a-variable-number-tandem-repeat-in-the-cyp2c9-promoter-on-wa-peer-reviewed-article-PGPM |
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