Journal of clinical lipidology最新文献

{"title":"Choosing the optimal nonstatin lipid lowering therapies for statin-intolerant patients: A systematic review and network meta-analysis.","authors":"Wattakorn Laohapiboolrattana, Paisit Kosum, Mantiwee Nimworapan, Piyameth Dilokthornsakul, Kansak Boonpattharatthiti, Nonthikorn Theerasuwipakorn, Duangnapa Roongpiboonsopit, Pattamawan Kosuma, Teerapon Dhippayom","doi":"10.1016/j.jacl.2025.07.012","DOIUrl":"https://doi.org/10.1016/j.jacl.2025.07.012","url":null,"abstract":"<p><strong>Background: </strong>Statin intolerance presents a considerable challenge in managing patients at risk for cardiovascular diseases, as it limits patients' access to standard lipid-lowering therapies.</p><p><strong>Objective: </strong>This study aims to compare the efficacy and safety of various nonstatin lipid-lowering therapies in patients who are intolerant to statins.</p><p><strong>Methods: </strong>We searched PubMed, Embase, CENTRAL, and EBSCO open dissertations through September 2023 for randomized controlled trials in statin-intolerant patients comparing nonstatin lipid-lowering agents. The primary outcome was low-density lipoprotein cholesterol (LDL-C). A random-effects model estimated comparative effects using mean differences (MDs) for LDL-C reduction and relative risks (RRs) for safety outcomes, specifically trial withdrawal due to adverse events. Results were reported with 95% CIs, and therapies ranked using the surface under the cumulative ranking curve (SUCRA). Evidence certainty was assessed with the Confidence in Network Meta-Analysis (CINeMA) platform.</p><p><strong>Results: </strong>Of 1533 articles, 6 studies (1326 patients) met inclusion criteria. Evolocumab combined with ezetimibe achieved the greatest LDL-C reduction (MD: 48.98%; 95% CI: 59.19, -38.77) vs ezetimibe alone, with moderate evidence certainty. Evolocumab, alirocumab, and the combination of bempedoic acid and ezetimibe, also showed significant reductions in LDL-C compared to ezetimibe monotherapy, though the magnitude of their effects was smaller than that of the evolocumab and ezetimibe combination. The SUCRA of evolocumab and ezetimibe (99.7%) aligns with its highest comparative efficacy. No significant differences in safety outcomes were observed across treatments.</p><p><strong>Conclusion: </strong>Evolocumab combined with ezetimibe is the most effective regimen for LDL-C reduction, with a safety profile comparable to other treatments, making it a viable alternative for patients with statin intolerance.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144992490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Experiences of people with elevated lipoprotein(a) and the impact on family and child screening.","authors":"Gabrielle Eversole, Sara M Fitzgerald-Butt, Colin Halverson, Julie M Clary, Benjamin M Helm","doi":"10.1016/j.jacl.2025.07.011","DOIUrl":"https://doi.org/10.1016/j.jacl.2025.07.011","url":null,"abstract":"<p><strong>Background: </strong>Lipoprotein(a) [Lp(a)] is a common heritable causal cardiovascular risk factor, and understanding how patients use Lp(a) status for family screening is imperative. No studies to date have focused on the patient's perspective of their experiences.</p><p><strong>Objective: </strong>To understand the experiences of people with elevated Lp(a), we investigated the factors that influence decision regret, optimism, anxiety, and family screening.</p><p><strong>Methods: </strong>Participants with self-reported elevated Lp(a) completed an online survey assessing their experiences living with elevated Lp(a), including demographics, clinical and family history, barriers to testing, and, among the parent sub-cohort, the decision to test children's Lp(a).</p><p><strong>Results: </strong>Among 1001 participants with completed surveys, most had no decision regret (70.7%) and minimal anxiety (71.7%) related to their elevated Lp(a). Almost half of participants (47.4%) experienced barriers to Lp(a) testing. Almost all participants (92.9%) reported they shared their Lp(a) results with their family. In a subgroup analysis of parents of children <18 years (n = 399), we investigated influences on the decision to test their children's Lp(a). Significant influences included age, optimism with current clinical care, and an interaction between decision regret and being clinically diagnosed with familial hypercholesterolemia (FH). Higher decision regret was associated with a lower probability of testing their children's Lp(a) for participants without a clinical diagnosis of FH.</p><p><strong>Conclusion: </strong>We report novel experiences of people with elevated Lp(a), including levels of Lp(a)-specific anxiety, optimism, and decision regret regarding testing. Our results provide impetus for future research aimed at improving Lp(a) testing access, clinician education, and providing support to patients and families.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Self-medication to lower LDL cholesterol and to treat statin-associated muscle symptoms in patients with statin intolerance.","authors":"Paulina E Stürzebecher, Julius L Katzmann, Ioanna Gouni-Berthold, Irina Müller-Kozarez, Christina Mateev, Ole Frenzel, Oliver Weingärtner, Ursula Kassner, Ulrike Schatz, Ulrich Laufs","doi":"10.1016/j.jacl.2025.07.009","DOIUrl":"https://doi.org/10.1016/j.jacl.2025.07.009","url":null,"abstract":"<p><strong>Background: </strong>Self-medication with supplements or over-the-counter drugs is very frequent despite limited evidence on efficacy and safety. Patients with statin intolerance (SI) may be prone to self-medication to lower low-density lipoprotein cholesterol (LDL-C) and to treat statin-associated muscle symptoms (SAMS).</p><p><strong>Objective: </strong>To evaluate the use and predictors of self-medication in the prospective, multicenter Statin Intolerance Registry at baseline.</p><p><strong>Methods and results: </strong>Among 1111 patients (mean age 66.1 [9.9] years, 57.7% female), 67.2% reported use of self-medication to lower LDL-C (43.8%, n = 487) or to treat SAMS (53.2%, n = 592). The most frequent self-medications used to treat SAMS were pain medication (31.1%), electrolytes (25.9%), and vitamin D (23.0%). The most commonly used supplements to lower LDL-C were omega-3 fatty acids (28.8%) and ginger/garlic (17.6%). Reporting self-medication was strongly associated with depressive symptoms (patient health questionnaire [PHQ-9] score) and experience of negative statin-related information. Use of self-medication to lower LDL-C was not associated with lower LDL-C levels. More than half (54.0%) of the patients reported negative statin-related influence from other people (mainly family and friends), the media, or both, which was associated with more frequent self-medication but similar LDL-C concentrations.</p><p><strong>Conclusions: </strong>The majority of patients with SI used self-medication to lower LDL-C or to treat SAMS. Self-medication was not associated with lower LDL-C levels. Proactive communication and education on the limited efficacy and safety of supplements may be needed to support the utilization of lipid-lowering medications with proven cardiovascular benefits.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brief communication: Strong concordance of the North American Familial Chylomicronemia Syndrome Score with a positive genetic diagnosis in patients from the Balance study.","authors":"Alan S Brown, Philippe Moulin, Andrew Dibble, Veronica J Alexander, Lu Li, Daniel Gaudet, Joseph L Witztum, Sotirios Tsimikas, Robert A Hegele","doi":"10.1016/j.jacl.2025.07.008","DOIUrl":"https://doi.org/10.1016/j.jacl.2025.07.008","url":null,"abstract":"<p><strong>Background: </strong>Patients with familial chylomicronemia syndrome (FCS) are often misdiagnosed. A positive genetic diagnosis is considered definitive, but clinical scoring systems can also identify affected patients. The North American FCS (NAFCS) Score is intended to identify patients likely to have positive DNA testing, but its sensitivity has not been quantified.</p><p><strong>Objective: </strong>To evaluate NAFCS Scores in patients from the Balance study.</p><p><strong>Methods: </strong>We calculated NAFCS Scores in 66 patients with genetically confirmed FCS from the Balance study of olezarsen.</p><p><strong>Results: </strong>We found that 95.5% (63/66) and 74.2% (49/66) of patients had NAFCS Scores ≥45 (\"likely FCS\") and ≥60 (\"definite FCS\"), respectively. In contrast, no patient had a score <30 (\"unlikely FCS\"), while 4.5% (3/66) had scores between 30 and 44 (\"uncertain FCS\").</p><p><strong>Conclusion: </strong>The strong concordance between NAFCS Score ≥45 and a positive genetic diagnosis of FCS suggests that either approach can be used for diagnosis except in \"uncertain FCS\" cases, which require genetic testing. The score might also clinically support an FCS diagnosis when genetic testing is indeterminate due to variants of unknown significance.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of pemafibrate on high-density lipoprotein cholesterol levels and subspecies in a patient with cholesteryl ester transfer protein deficiency: A case report with mechanistic insights.","authors":"Ryohei Tanigawa, So Nagai, Hirokazu Takahashi, Hideki Suganami, Shizuya Yamashita","doi":"10.1016/j.jacl.2025.07.006","DOIUrl":"https://doi.org/10.1016/j.jacl.2025.07.006","url":null,"abstract":"<p><p>Cholesteryl ester transfer protein (CETP) deficiency is a representative molecular abnormality in familial hyperalphalipoproteinemia, a hereditary disorder of lipid metabolism characterized by markedly elevated plasma high-density lipoprotein cholesterol (HDL-C) levels. In this condition, dysfunction of CETP, which mediates the transfer of cholesteryl esters from HDL particles to apolipoprotein (Apo)B-containing lipoproteins, leads to the abnormal accumulation of HDL-C. These HDL particles are unusually large and enriched in cholesteryl esters, ApoCIII, and ApoE, whereas low-density lipoprotein (LDL) particles are small, depleted of cholesteryl esters, and enriched in triglycerides. Both HDL and LDL particles in CETP deficiency are functionally abnormal. Pemafibrate, a selective peroxisome proliferator-activated receptor α modulator, has consistently been demonstrated in clinical trials to increase HDL-C levels by 16% to 22% in patients with dyslipidemia and low baseline HDL-C. Herein, we describe the unexpected finding of a marked reduction in HDL-C levels in a patient with CETP deficiency following pemafibrate treatment. To better understand this paradoxical response, we analyzed the patient's clinical data and investigated potential mechanisms underlying pemafibrate's effects on HDL metabolism.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of evinacumab in patients with severe hypertriglyceridemia and a history of severe hypertriglyceridemia-related acute pancreatitis: A phase 2b trial.","authors":"Robert S Rosenson, Richard T George, Robert J Sanchez, Xue-Qiao Zhao, Manish P Ponda, Alpana Waldron, Robert Pordy","doi":"10.1016/j.jacl.2025.07.005","DOIUrl":"https://doi.org/10.1016/j.jacl.2025.07.005","url":null,"abstract":"<p><strong>Background: </strong>Severe hypertriglyceridemia (sHTG) is an established risk factor for acute pancreatitis (AP).</p><p><strong>Objective: </strong>To evaluate the efficacy of a 20 mg/kg dose of intravenous evinacumab vs placebo on sHTG-associated episodes of AP.</p><p><strong>Methods: </strong>This phase 2b study (NCT04863014) enrolled adults with sHTG and a history of hypertriglyceridemia-associated AP. Eligible patients were randomly assigned to intravenous evinacumab 20 mg/kg or placebo every 4 weeks over a 52-week double-blind treatment period.</p><p><strong>Results: </strong>Forty patients were screened; 21 patients received either evinacumab (n = 11) or placebo (n = 10). Twelve (57.1%) patients completed the study. The proportion of patients with ≥1 positively adjudicated AP episode during the 52-week treatment period (primary endpoint) was 27.3% (n = 3) with evinacumab vs 10.0% (n = 1) with placebo. All positively adjudicated AP episodes occurred ≥58 days after the last evinacumab dose, when evinacumab concentrations were mostly near or below the limit of quantitation. The median percentage change in triglycerides from baseline to week 4 was -55.3% with evinacumab vs +1.5% with placebo. By week 16, evinacumab reduced triglycerides by 95.7%; the effect was maintained in 1 patient who received treatment through week 52. Incidence of treatment-emergent adverse events was lower with evinacumab (63.6%) than with placebo (100.0%).</p><p><strong>Conclusion: </strong>Although the sample size was too small to determine whether evinacumab can prevent AP, the data suggest evinacumab may be efficacious in lowering triglyceride concentrations in patients with sHTG and a history of sHTG-associated AP. Tolerability and safety of evinacumab was consistent with previous studies.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obicetrapib and its impact on lipid parameters: A comprehensive meta-analysis of the latest evidence.","authors":"Muhammad Imaz Bhatti, Muhammad Safiullah, Kanza Farhan, Ahmad Ali, Sofia Abdullah, Ahmed Ali, Raheel Ahmed","doi":"10.1016/j.jacl.2025.07.003","DOIUrl":"https://doi.org/10.1016/j.jacl.2025.07.003","url":null,"abstract":"<p><strong>Background: </strong>Dyslipidemia remains a central contributor to residual cardiovascular risk despite the widespread use of statins. Obicetrapib, a selective cholesteryl ester transfer protein (CETP) inhibitor, has shown potential as an adjunctive lipid-lowering therapy by favorably modifying key lipid parameters. This study aimed to systematically evaluate the lipid-lowering efficacy of obicetrapib based on current evidence from randomized controlled trials (RCTs).</p><p><strong>Sources of material: </strong>A comprehensive literature search was conducted on PubMed, Embase, Scopus, and ClinicalTrials.gov to identify RCTs assessing the lipid-lowering effects of obicetrapib. Mean differences (MDs) with 95% CIs were calculated using a random-effects model.</p><p><strong>Abstract of findings: </strong>Nine RCTs (n = 3706) were included. Patients treated with obicetrapib exhibited significant reductions in low-density lipoprotein cholesterol (LDL-C) (MD: -36.5% [95% CI: -41.1 to -31.9]), apolipoprotein B (Apo-B) (MD: -23.8% [95% CI: -28.2 to -19.3]), non-high-density lipoprotein cholesterol (non-HDL-C) (MD: -30.9% [95% CI: -34.6 to -27.1]), and lipoprotein (a) [Lp(a)] (MD: -36.1% [95% CI: -44.4 to -27.8]) compared to placebo. High-density lipoprotein cholesterol (HDL-C) levels significantly increased (MD: 142.6% [95% CI: 128.6-156.6]). Triglyceride levels did not differ significantly (MD: 0.13% [95% CI: -7.01 to 7.26]). Moreover, combination therapy with ezetimibe led to greater reductions in LDL-C by 17.8% (95% CI: 12.05-23.6), Apo-B by 9.7% (95% CI: 5.8-13.7), and non-HDL-C by 17.5% (95% CI: 12.3-22.8), compared to monotherapy.</p><p><strong>Conclusion: </strong>Obicetrapib significantly improves key lipid parameters, including LDL-C, Apo-B, non-HDL-C, HDL-C, and Lp(a), with enhanced efficacy in lowering LDL-C, Apo-B, and non-HDL-C when combined with ezetimibe. These findings support its potential role in comprehensive lipid management strategies.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144846657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelial function in high-risk patients with ezetimibe therapy.","authors":"Merve Günes-Altan, Agnes Bosch, Kristina Striepe, Mario Schiffer, Stephan Achenbach, Roland E Schmieder, Dennis Kannenkeril","doi":"10.1016/j.jacl.2025.07.001","DOIUrl":"https://doi.org/10.1016/j.jacl.2025.07.001","url":null,"abstract":"<p><strong>Background: </strong>Impaired endothelial function predicts cardiovascular (CV) events, even in patients with established atherosclerotic CV disease (ASCVD). The aim of this post hoc analysis was to compare the endothelial function between high-risk patients on optimized statin therapy with and without additional ezetimibe treatment.</p><p><strong>Methods: </strong>A total of 91 patients with ASCVD and statin treatment (atorvastatin or rosuvastatin) were included and underwent examination of endothelial function by the UNEX EF device. Endothelial function parameters were compared between patients with ezetimibe (E+ group) and without ezetimibe therapy (E- group) (NCT03626831).</p><p><strong>Results: </strong>Compared to patients in the E- group (n = 70), patients in the E+ group (n = 21) were younger (67.0 ± 7.4 vs 61.2 ± 7.2 years; P = .002), had lower low-density lipoprotein cholesterol (91.2 ± 13.3 vs 102.0 ± 18.1 mg/dL (P = .013) and lower office systolic blood pressure (123.9 ± 11.4 vs 130.2 ± 14.5 mm Hg (P = .042). High-sensitivity C-reactive protein (hsCRP) was lower in the E+ group than in the E- group (0.5 ± 0.4 vs 1.1 ± 0.9 mg/L; P = .037). We found a greater flow-mediated vasodilation (FMD) (6.1 ± 2.0 vs 3.7 ± 3.2%; P = .004) and lower brachial intima-media thickness (0.28 ± 0.1 vs 0.32 ± 0 mm; P = .011) in the E+ group compared to the E- group. When confounders were entered in a covariance analysis, the differences in FMD (P = .034) and hsCRP (P = .049) between the groups remained significant.</p><p><strong>Conclusion: </strong>In this cross-sectional analysis, we observed a difference of FMD suggesting potentially better endothelial function in high-risk ASCVD patients on ezetimibe plus statin compared to statin monotherapy; however, causal conclusions cannot be drawn.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Major lipoprotein(a) increase under IGF-1R inhibition in Graves' orbitopathy: A case report.","authors":"Maxime Carpentier, Pierre-Olivier Bertho, Pierre Lebranchu, Delphine Drui, Bertrand Cariou","doi":"10.1016/j.jacl.2025.07.002","DOIUrl":"https://doi.org/10.1016/j.jacl.2025.07.002","url":null,"abstract":"<p><p>Elevated plasma lipoprotein(a) [Lp(a)] is an independent cardiovascular risk factor due to its strong link with atherosclerotic cardiovascular disease. Although Lp(a) levels are mainly genetically determined and stable, conditions such as Graves' disease, which causes hyperthyroidism, can reduce Lp(a) concentration by 20% to 35%. Graves' orbitopathy (GO), a common manifestation of Graves' disease, is characterized by the interplay between thyroid-stimulating hormone (TSH) and insulin-like growth factor-1 (IGF-1) signaling. Clinical trials have shown that teprotumumab, an IGF-1 receptor inhibiting monoclonal antibody, improves GO outcomes. Since IGF-1 is known to decrease Lp(a) by 40% to 80%, its blockade by teprotumumab may disrupt Lp(a) metabolism and lead to adverse metabolic effects. Here we report the case of a 74-year-old woman with GO who experienced a significant increase in Lp(a) levels exceeding the atherogenic threshold (ie, > 125 nmol/L) following teprotumumab therapy. These variations of Lp(a) levels occur independently of thyroid homeostasis. This clinical observation underlines the importance of monitoring Lp(a) concentrations during treatment with IGF-1 inhibitors, particularly in patients at high cardiovascular risk.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotypic and molecular characterization of the exon 13-15 duplication in LDLR: Implications for familial hypercholesterolemia.","authors":"Diego Abarzúa, Claudia Radojkovic, Santiago Quintana, Catalina Martínez, Natalia Barriga, Rodrigo Alonso, Enrique Guzman, Carlos Felipe Burgos, Andrea Sánchez","doi":"10.1016/j.jacl.2025.06.023","DOIUrl":"https://doi.org/10.1016/j.jacl.2025.06.023","url":null,"abstract":"<p><strong>Background: </strong>Familial hypercholesterolemia (FH) is an inherited disorder characterized by elevated levels of low-density lipoprotein (LDL) cholesterol, significantly increasing the risk of premature cardiovascular disease. Major rearrangements were among the first mutations identified in the low-density lipoprotein receptor (LDLR) gene and currently comprise approximately 10% of FH-causing variants. One of them is the exon13_15dup. However, the impact on the structure and function of the LDLR is poorly understood.</p><p><strong>Objective: </strong>To determine the structural and functional impact of the exon13_15dup variant in the LDLR gene in FH patients.</p><p><strong>Methods: </strong>The RNA extracted from CD14+ macrophage differentiation was obtained from non-consanguineous index cases carrying this mutation. Polymerase chain reaction and Sanger evaluated the junction sequence of the mutation sequenced. The obtained sequences were used to construct in silico models and perform molecular dynamics assays.</p><p><strong>Results: </strong>The exon13_15dup variant resulted in substantial structural alterations within the LDLR, producing a truncated protein lacking both the transmembrane and cytoplasmic domains.</p><p><strong>Conclusions: </strong>The structural changes caused by the exon13_15dup variant significantly impair the functionality of the LDLR protein, contributing to the clinical phenotype observed in patients with FH.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}