دورية أكاديمية
أعرض في EDS

SLCO1B1 Exome Sequencing and Statin Treatment Response in 64,000 UK Biobank Patients.

التفاصيل البيبلوغرافية
العنوان: SLCO1B1 Exome Sequencing and Statin Treatment Response in 64,000 UK Biobank Patients.
المؤلفون: Türkmen D; Epidemiology & Public Health Group, Department of Clinical & Biomedical Science, Faculty of Health & Life Sciences, University of Exeter, Exeter EX4 4QD, UK., Bowden J; Exeter Diabetes Group (ExCEED), Department of Clinical & Biomedical Science, Faculty of Health & Life Sciences, University of Exeter, Exeter EX4 4QD, UK.; Department of Genetics, Novo Nordisk Research Centre Oxford, Innovation Building, Old Road Campus, Oxford OX3 7BN, UK., Masoli JAH; Epidemiology & Public Health Group, Department of Clinical & Biomedical Science, Faculty of Health & Life Sciences, University of Exeter, Exeter EX4 4QD, UK.; Department of Healthcare for Older People, Royal Devon University Healthcare NHS Foundation Trust, Exeter EX2 5DW, UK., Melzer D; Epidemiology & Public Health Group, Department of Clinical & Biomedical Science, Faculty of Health & Life Sciences, University of Exeter, Exeter EX4 4QD, UK., Pilling LC; Epidemiology & Public Health Group, Department of Clinical & Biomedical Science, Faculty of Health & Life Sciences, University of Exeter, Exeter EX4 4QD, UK.
المصدر: International journal of molecular sciences [Int J Mol Sci] 2024 Apr 17; Vol. 25 (8). Date of Electronic Publication: 2024 Apr 17.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, [2000-
مواضيع طبية MeSH: Exome Sequencing*/methods , Hydroxymethylglutaryl-CoA Reductase Inhibitors*/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors*/adverse effects , Liver-Specific Organic Anion Transporter 1*/genetics, Aged ; Female ; Humans ; Male ; Middle Aged ; Atorvastatin/therapeutic use ; Polymorphism, Single Nucleotide ; Simvastatin/therapeutic use ; Treatment Outcome ; UK Biobank ; United Kingdom
مستخلص: The solute carrier organic anion transporter family member 1B1 ( SLCO1B1 ) encodes the organic anion-transporting polypeptide 1B1 (OATP1B1 protein) that transports statins to liver cells. Common genetic variants in SLCO1B1 , such as *5, cause altered systemic exposure to statins and therefore affect statin outcomes, with potential pharmacogenetic applications; yet, evidence is inconclusive. We studied common and rare SLCO1B1 variants in up to 64,000 patients from UK Biobank prescribed simvastatin or atorvastatin, combining whole-exome sequencing data with up to 25-year routine clinical records. We studied 51 predicted gain/loss-of-function variants affecting OATP1B1. Both SLCO1B1 *5 alone and the SLCO1B1 *15 haplotype increased LDL during treatment (beta*5 = 0.08 mmol/L, p = 6 × 10 -8 ; beta*15 = 0.03 mmol/L, p = 3 × 10 -4 ), as did the likelihood of discontinuing statin prescriptions (hazard ratio*5 = 1.12, p = 0.04; HR*15 = 1.05, p = 0.04). SLCO1B1 *15 and SLCO1B1 *20 increased the risk of General Practice (GP)-diagnosed muscle symptoms (HR*15 = 1.22, p = 0.003; HR*20 = 1.25, p = 0.01). We estimated that genotype-guided prescribing could potentially prevent 18% and 10% of GP-diagnosed muscle symptoms experienced by statin patients, with *15 and *20, respectively. The remaining common variants were not individually significant. Rare variants in SLCO1B1 increased LDL in statin users by up to 1.05 mmol/L, but replication is needed. We conclude that genotype-guided treatment could reduce GP-diagnosed muscle symptoms in statin patients; incorporating further SLCO1B1 variants into clinical prediction scores could improve LDL control and decrease adverse events, including discontinuation.
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معلومات مُعتمدة: MR/X011372/1 United Kingdom MRC_ Medical Research Council
فهرسة مساهمة: Keywords: SLCO1B1; cholesterol; clinical response; epidemiology; exome sequencing variants; pharmacogenomics; statin
المشرفين على المادة: A0JWA85V8F (Atorvastatin)
0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
0 (Liver-Specific Organic Anion Transporter 1)
AGG2FN16EV (Simvastatin)
0 (SLCO1B1 protein, human)
تواريخ الأحداث: Date Created: 20240427 Date Completed: 20240427 Latest Revision: 20240724
رمز التحديث: 20240726
مُعرف محوري في PubMed: PMC11050003
DOI: 10.3390/ijms25084426
PMID: 38674010
قاعدة البيانات: MEDLINE
الوصف
تدمد:1422-0067
DOI:10.3390/ijms25084426