TY - JOUR
T1 - Transporter Genes and statin-induced Hepatotoxicity
AU - Choi, Seo A.
AU - Kim, Jung Sun
AU - Park, Yoon A.
AU - Lee, Da Hoon
AU - Park, Minju
AU - Yee, Jeong
AU - Chang, Yoonkyung
AU - Song, Tae Jin
AU - Gwak, Hye Sun
N1 - Publisher Copyright:
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024.
PY - 2024
Y1 - 2024
N2 - Purpose: Hepatotoxicity has emerged as a major cause of statin treatment interruption. Although organic anion-transporting polypeptide 1B1 (SLCO1B1), multidrug resistance protein 1 (ABCB1), and breast cancer resistance protein (ABCG2) have been identified as transporters of statins, knowledge of their role in statin-associated hepatotoxicity remains limited. Therefore, we aimed to conduct a comprehensive analysis to elucidate the association between hepatotoxicity and SLCO1B1, ABCB1, and ABCG2 polymorphisms. Methods: This study retrospectively analyzed prospectively collected samples. We selected 10 single nucleotide polymorphisms (SNPs) of SLCO1B1, 9 SNPs of ABCB1, and 12 SNPs of ABCG2. We developed two models for multivariable analyses (Model I: clinical factors only; Model II: both clinical and genetic factors), and the attributable risk (%) of variables in Model II was determined. Results: Among 851 patients, 66 (7.8%) developed hepatotoxicity. In Model I, lipophilic statins, atrial fibrillation (Afib), and diabetes mellitus showed a significant association with hepatotoxicity. In Model II, lipophilic statins and Afib, SLCO1B1 rs11045818 A allele, SLCO1B1 rs4149035 T allele, and ABCG2 rs2622629 TT genotype were associated with higher hepatotoxicity risk. Among them, the SLCO1B1 rs11045818 A allele exhibited the highest attributable risk (93.2%). The area under the receiver operating characteristic curve in Model I was 0.62 (95% CI: 0.55–0.69), and it was increased to 0.71 in Model II (95% CI: 0.64–0.77). Conclusion: This study investigated the correlation between hepatotoxicity and polymorphisms of transporter genes in patients taking statins. The findings could help improve personalized treatments for patients receiving statin therapy.
AB - Purpose: Hepatotoxicity has emerged as a major cause of statin treatment interruption. Although organic anion-transporting polypeptide 1B1 (SLCO1B1), multidrug resistance protein 1 (ABCB1), and breast cancer resistance protein (ABCG2) have been identified as transporters of statins, knowledge of their role in statin-associated hepatotoxicity remains limited. Therefore, we aimed to conduct a comprehensive analysis to elucidate the association between hepatotoxicity and SLCO1B1, ABCB1, and ABCG2 polymorphisms. Methods: This study retrospectively analyzed prospectively collected samples. We selected 10 single nucleotide polymorphisms (SNPs) of SLCO1B1, 9 SNPs of ABCB1, and 12 SNPs of ABCG2. We developed two models for multivariable analyses (Model I: clinical factors only; Model II: both clinical and genetic factors), and the attributable risk (%) of variables in Model II was determined. Results: Among 851 patients, 66 (7.8%) developed hepatotoxicity. In Model I, lipophilic statins, atrial fibrillation (Afib), and diabetes mellitus showed a significant association with hepatotoxicity. In Model II, lipophilic statins and Afib, SLCO1B1 rs11045818 A allele, SLCO1B1 rs4149035 T allele, and ABCG2 rs2622629 TT genotype were associated with higher hepatotoxicity risk. Among them, the SLCO1B1 rs11045818 A allele exhibited the highest attributable risk (93.2%). The area under the receiver operating characteristic curve in Model I was 0.62 (95% CI: 0.55–0.69), and it was increased to 0.71 in Model II (95% CI: 0.64–0.77). Conclusion: This study investigated the correlation between hepatotoxicity and polymorphisms of transporter genes in patients taking statins. The findings could help improve personalized treatments for patients receiving statin therapy.
KW - ABCB1
KW - ABCG2
KW - Hepatotoxicity
KW - Pharmacogenomics
KW - SLCO1B1
KW - Statins
UR - http://www.scopus.com/inward/record.url?scp=85194706750&partnerID=8YFLogxK
U2 - 10.1007/s10557-024-07580-2
DO - 10.1007/s10557-024-07580-2
M3 - Article
AN - SCOPUS:85194706750
SN - 0920-3206
JO - Cardiovascular Drugs and Therapy
JF - Cardiovascular Drugs and Therapy
ER -