Dataset Information

Polymorphisms of SLCO1B1 rs4149056 and SLC22A1 rs2282143 are associated with responsiveness to acitretin in psoriasis patients.

ABSTRACT: Acitretin is widely used to treat psoriasis, but the efficacy varies significantly among individuals. To explore the association between polymorphisms and acitretin efficacy, we enrolled 46 and 105 Chinese Han psoriasis vulgaris patients for discovery and validation phases, respectively. The patients were treated with acitretin (30?mg/day) and calcipotriol ointment for at least 8 weeks, and their genotypes were detected. The wild-type genes and variants were transfected into HEK293 cells, which were then incubated with acitretin. The cellular acitretin concentration was measured by liquid chromatography-mass spectrometry. We found that the polymorphisms rs4149056 in the SLCO1B1 gene and rs2282143 in the SLC22A1 gene were associated with efficacy, both in the discovery (P?=?0.013 and P?=?0.002) and validation phases (P?=?0.028 and P?=?0.014), based on a 50% reduction from before to after treatment of the psoriasis area severity index (PASI50). When the PASI75 was used as an efficacy cutoff, a similar conclusion was drawn. The uptake of acitretin was lower with the rs4149056C (P?=?0.002) and rs2282143T alleles (P?=?0.038) than the wild-type alleles. Our results imply that the rs4149056C and rs2282143T variants decrease the acitretin uptake, and significantly associated with clinical effective responsiveness.

SUBMITTER: Chen W

PROVIDER: S-EPMC6123456 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Polymorphisms of SLCO1B1 rs4149056 and SLC22A1 rs2282143 are associated with responsiveness to acitretin in psoriasis patients.

Chen Wangqing W Zhang Xu X Zhang Wei W Peng Cong C Zhu Wu W Chen Xiang X

Scientific reports 20180904 1

Acitretin is widely used to treat psoriasis, but the efficacy varies significantly among individuals. To explore the association between polymorphisms and acitretin efficacy, we enrolled 46 and 105 Chinese Han psoriasis vulgaris patients for discovery and validation phases, respectively. The patients were treated with acitretin (30 mg/day) and calcipotriol ointment for at least 8 weeks, and their genotypes were detected. The wild-type genes and variants were transfected into HEK293 cells, which ...[more]

PMID: 30181619

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Project description:UnlabelledPatients with familial hypercholesterolemia (FH) may be at increased risk for statin-associated muscle symptoms because they require long-term treatment with high-intensity statin therapy. We sought to determine (1) whether other predisposing factors, including the well-known genetic variant associated with statin-associated muscle symptoms-solute carrier organic anion transporter family, member 1B1 (SLCO1B1) rs4149056-also increase the risk of statin-associated muscle symptoms in FH patients, and (2) the natural history and management for FH patients with statin-associated muscle symptoms.MethodsWe queried electronic records (2004-2014) of 278 genetically screened FH patients (113 men, 165 women; mean [SD] pretreatment low-density lipoprotein cholesterol [LDL-C] 259 [72] mg/dL) recruited from lipid clinics in the Dallas, TX, area from 2004 to 2014. Statin-associated muscle symptoms were defined as muscle symptoms arising while taking a statin and interrupting therapy.ResultsThe risk of muscle symptoms was associated with age (odds ratio 1.6 [95% CI 1.2-2.2]), body mass index in non-African Americans (0.90 [0.83-0.97]), and hypertension (0.4 [0.2-0.9]). Simvastatin was the most commonly used statin, and it was the statin most associated with muscle symptoms. Among FH patients with muscle symptoms, 41% (n = 40) reestablished statin therapy ("eventually tolerant") and 29% (n = 28) never reestablished statin therapy ("never tolerant"). Rosuvastatin (43%) and pravastatin (30%) were the most common eventually tolerated statins, and eventually tolerant patients achieved lower treated LDL-C levels (eventually tolerant 127 vs never tolerant 192 mg/dL, P < .001). Never tolerant patients also developed muscle symptoms on nonstatins (16% vs 50%, P = .003). SLCO1B1 rs4149056 genotyping revealed 224 wild-type patients (TT) and 49 heterozygotes (TC). SLCO1B1 genotype was not associated with the risk of statin-associated muscle symptoms (odds ratio 1.40 [95% CI 0.74-2.64]).ConclusionAge, not SLCO1B1 rs4149056 genotype, was the strongest risk factor for statin-associated muscle symptoms in FH patients. After developing muscle symptoms, many patients reestablished statin therapy and achieved significant LDL-C reductions. Overall, 10% of all FH patients had statin-associated muscle symptoms and never reestablished statin therapy. Such patients developed muscle symptoms even on nonstatin lipid-lowering drugs and continued to have elevations in LDL-C. Further insight is needed into the relationship between FH and statin-associated muscle symptoms so all FH patients can be adequately treated.

Dataset Information

Polymorphisms of SLCO1B1 rs4149056 and SLC22A1 rs2282143 are associated with responsiveness to acitretin in psoriasis patients.

Publications

Polymorphisms of SLCO1B1 rs4149056 and SLC22A1 rs2282143 are associated with responsiveness to acitretin in psoriasis patients.

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