Pharmacogenetic Study of the Impact of <i>ABCB1</i> Single Nucleotide Polymorphisms on the Response to Cyclosporine in Psoriasis Patients
Psoriasis is a chronic, T cell-mediated skin disease affecting 2–3% of the Caucasian population. Cyclosporine A is a calcineurin inhibitor that acts selectively on T cells. The cyclosporine A treatment response has been suggested to be modulated by single-nucleotide polymorphisms (SNPs) in the <i...
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MDPI AG
2022-11-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/11/2441 |
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| author | Alexandr Chernov Daria Kilina Tatiana Smirnova Elvira Galimova |
| author_facet | Alexandr Chernov Daria Kilina Tatiana Smirnova Elvira Galimova |
| author_sort | Alexandr Chernov |
| collection | DOAJ |
| description | Psoriasis is a chronic, T cell-mediated skin disease affecting 2–3% of the Caucasian population. Cyclosporine A is a calcineurin inhibitor that acts selectively on T cells. The cyclosporine A treatment response has been suggested to be modulated by single-nucleotide polymorphisms (SNPs) in the <i>ABCB1</i> gene. The aim of this research was to evaluate the effect of <i>ABCB1</i> genetic variants that could affect the response to a cyclosporine treatment in Russian psoriasis patients with the <i>ABCB1</i> genotype status. The <i>ABCB1</i> T-129C, G1199A, C1236T, G2677T/A and C3435T SNPs in the 168 patients with psoriasis were genotyped by PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) and TaqMan SNP genotyping assays. The <i>ABCB1</i> C1236T, G2677T/A and C3435T SNPs were significantly associated with a negative response to cyclosporine therapy. A very strong association was evident for the C3435T SNP in the <i>ABCB1</i> gene in the allele, dominant and recessive models (OR = 2.58, OR = 4.01, OR = 2.50, respectively). <i>ABCB1</i> C1236T and G2677T/A polymorphisms were significantly associated with a negative response to the cyclosporine therapy in the codominant, dominant and recessive models (<i>p</i> ˂ 0.05). Additionally, the haplotype analysis identified that the TGC haplotype is significantly associated with a negative response to cyclosporine therapy in psoriasis patients (<i>p</i> ˂ 0.05). The current study to the best of our knowledge is the first of its kind to be performed in the Russian population. In conclusion, the present results suggest an association between the <i>ABCB1</i> genetic variants and unresponsiveness to cyclosporine in the Russian population. Further, larger studies are necessary to confirm our findings and replicate them in various ethnic populations before its implementation in the clinical practice. |
| first_indexed | 2024-03-09T18:04:52Z |
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| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T18:04:52Z |
| publishDate | 2022-11-01 |
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| spelling | doaj.art-c5d1bf042f74485c966fa8969662452e2023-11-24T09:35:54ZengMDPI AGPharmaceutics1999-49232022-11-011411244110.3390/pharmaceutics14112441Pharmacogenetic Study of the Impact of <i>ABCB1</i> Single Nucleotide Polymorphisms on the Response to Cyclosporine in Psoriasis PatientsAlexandr Chernov0Daria Kilina1Tatiana Smirnova2Elvira Galimova3Department of Life Sciences, Ben-Gurion University, Beer Sheva 84105, IsraelHLA Laboratory, V.A. Almazov National Medical Research Center of the Ministry of Health of Russia, St. Petersburg 197341, RussiaCity Dispensary of Dermatology and Venereology, St. Petersburg 192102, RussiaInterdisciplinary Laboratory for Neurobiology, Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg 194223, RussiaPsoriasis is a chronic, T cell-mediated skin disease affecting 2–3% of the Caucasian population. Cyclosporine A is a calcineurin inhibitor that acts selectively on T cells. The cyclosporine A treatment response has been suggested to be modulated by single-nucleotide polymorphisms (SNPs) in the <i>ABCB1</i> gene. The aim of this research was to evaluate the effect of <i>ABCB1</i> genetic variants that could affect the response to a cyclosporine treatment in Russian psoriasis patients with the <i>ABCB1</i> genotype status. The <i>ABCB1</i> T-129C, G1199A, C1236T, G2677T/A and C3435T SNPs in the 168 patients with psoriasis were genotyped by PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) and TaqMan SNP genotyping assays. The <i>ABCB1</i> C1236T, G2677T/A and C3435T SNPs were significantly associated with a negative response to cyclosporine therapy. A very strong association was evident for the C3435T SNP in the <i>ABCB1</i> gene in the allele, dominant and recessive models (OR = 2.58, OR = 4.01, OR = 2.50, respectively). <i>ABCB1</i> C1236T and G2677T/A polymorphisms were significantly associated with a negative response to the cyclosporine therapy in the codominant, dominant and recessive models (<i>p</i> ˂ 0.05). Additionally, the haplotype analysis identified that the TGC haplotype is significantly associated with a negative response to cyclosporine therapy in psoriasis patients (<i>p</i> ˂ 0.05). The current study to the best of our knowledge is the first of its kind to be performed in the Russian population. In conclusion, the present results suggest an association between the <i>ABCB1</i> genetic variants and unresponsiveness to cyclosporine in the Russian population. Further, larger studies are necessary to confirm our findings and replicate them in various ethnic populations before its implementation in the clinical practice.https://www.mdpi.com/1999-4923/14/11/2441pharmacogeneticspsoriasiscyclosporineunresponsivenessABCB1 genepolymorphisms |
| spellingShingle | Alexandr Chernov Daria Kilina Tatiana Smirnova Elvira Galimova Pharmacogenetic Study of the Impact of <i>ABCB1</i> Single Nucleotide Polymorphisms on the Response to Cyclosporine in Psoriasis Patients Pharmaceutics pharmacogenetics psoriasis cyclosporine unresponsiveness ABCB1 gene polymorphisms |
| title | Pharmacogenetic Study of the Impact of <i>ABCB1</i> Single Nucleotide Polymorphisms on the Response to Cyclosporine in Psoriasis Patients |
| title_full | Pharmacogenetic Study of the Impact of <i>ABCB1</i> Single Nucleotide Polymorphisms on the Response to Cyclosporine in Psoriasis Patients |
| title_fullStr | Pharmacogenetic Study of the Impact of <i>ABCB1</i> Single Nucleotide Polymorphisms on the Response to Cyclosporine in Psoriasis Patients |
| title_full_unstemmed | Pharmacogenetic Study of the Impact of <i>ABCB1</i> Single Nucleotide Polymorphisms on the Response to Cyclosporine in Psoriasis Patients |
| title_short | Pharmacogenetic Study of the Impact of <i>ABCB1</i> Single Nucleotide Polymorphisms on the Response to Cyclosporine in Psoriasis Patients |
| title_sort | pharmacogenetic study of the impact of i abcb1 i single nucleotide polymorphisms on the response to cyclosporine in psoriasis patients |
| topic | pharmacogenetics psoriasis cyclosporine unresponsiveness ABCB1 gene polymorphisms |
| url | https://www.mdpi.com/1999-4923/14/11/2441 |
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