Scholarlink

Background <p>The SLCO1B1 c.521&#xa0;T &gt; C variant, which reduces hepatic statin uptake, has been linked to an increased risk of statin-associated muscle symptoms (SAMS), particularly with simvastatin. This study aimed to assess its association with SAMS and prescription of contemporary lipid-lowering therapy in patients with severe hypercholesterolemia.</p> Methods and results <p>We included 219 patients with a mean age of 53.9 ± 12.7&#xa0;years who attended our outpatient lipid clinic and were genotyped for the SLCO1B1 c.521&#xa0;T &gt; C variant. Treating physicians and patients were unaware of genotyping results. Six patients (2.7%) were homozygous and 68 patients (31.1%) were heterozygous for the c.521&#xa0;T &gt; C variant. After treatment optimization, the median LDL cholesterol levels were 63 (IQR 40–124) mg/dL and 74 (IQR 43–129) mg/dL in mutation carriers and non-carriers, respectively (<i>p</i> = 0.35). Self-reported SAMS did not differ between mutation carriers and non-carriers (25.7% vs. 27.6%; <i>p</i> = 0.76). In addition, statin usage (70.3% vs. 73.1%; <i>p</i> = 0.66) and prescription rates of proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK9i) (32.4% vs. 31.0%; <i>p</i> = 0.83) did not differ according to mutation status.</p> Discussion <p>In patients with severe hypercholesterolemia on contemporary statin therapy, the SLCO1B1 c.521&#xa0;T &gt; C variant was not associated with SAMS, reduced statin use, or increased prescription of PCSK9 inhibitors. The SLCO1B1 c.521&#xa0;T &gt; C variant appears to have no clear clinical relevance, but testing for it may potentially be harmful, as fear of side effects could result in statin undertreatment.</p> Graphical Abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

The SLCO1B1 c.521 T>C variant (rs4149056) is not associated with muscular symptoms or PCSK9-inhibitor prescription in patients with severe hypercholesterolemia and contemporary lipid lowering therapy

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月30日

查看全文
  • Lukas Galli,
  • Johannes Bernhard,
  • Iris E. Undt,
  • Patrick Haider,
  • Christian Hengstenberg,
  • Konstantin A. Krychtiuk,
  • Walter S. Speidl

摘要

Background

The SLCO1B1 c.521 T > C variant, which reduces hepatic statin uptake, has been linked to an increased risk of statin-associated muscle symptoms (SAMS), particularly with simvastatin. This study aimed to assess its association with SAMS and prescription of contemporary lipid-lowering therapy in patients with severe hypercholesterolemia.

Methods and results

We included 219 patients with a mean age of 53.9 ± 12.7 years who attended our outpatient lipid clinic and were genotyped for the SLCO1B1 c.521 T > C variant. Treating physicians and patients were unaware of genotyping results. Six patients (2.7%) were homozygous and 68 patients (31.1%) were heterozygous for the c.521 T > C variant. After treatment optimization, the median LDL cholesterol levels were 63 (IQR 40–124) mg/dL and 74 (IQR 43–129) mg/dL in mutation carriers and non-carriers, respectively (p = 0.35). Self-reported SAMS did not differ between mutation carriers and non-carriers (25.7% vs. 27.6%; p = 0.76). In addition, statin usage (70.3% vs. 73.1%; p = 0.66) and prescription rates of proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK9i) (32.4% vs. 31.0%; p = 0.83) did not differ according to mutation status.

Discussion

In patients with severe hypercholesterolemia on contemporary statin therapy, the SLCO1B1 c.521 T > C variant was not associated with SAMS, reduced statin use, or increased prescription of PCSK9 inhibitors. The SLCO1B1 c.521 T > C variant appears to have no clear clinical relevance, but testing for it may potentially be harmful, as fear of side effects could result in statin undertreatment.

Graphical Abstract