Journal of clinical lipidology最新文献

{"title":"A case of lipoprotein glomerulopathy due to the pathogenic APOE Las Vegas variant c.509C > A: p. (Ala170Asp)","authors":"Janneke W.C.M. Mulder MD ,&nbsp;Naomi ‘t Hart BSc ,&nbsp;Monique T. Mulder PhD ,&nbsp;Linda Zuurbier PhD ,&nbsp;Jeanine E. Roeters van Lennep MD, PhD","doi":"10.1016/j.jacl.2024.11.009","DOIUrl":"10.1016/j.jacl.2024.11.009","url":null,"abstract":"<div><div>This report describes a rare case of lipoprotein glomerulopathy. A 63-year-old man presented with nephrotic syndrome unresponsive to rituximab and tacrolimus. Blood tests showed a mild- to moderate hypertriglyceridemia suggesting familial dysbetalipoproteinemia (FD). Additional diagnostic procedures including lipoprotein ultracentrifugation, fast protein liquid chromatography and agarose gel electrophoresis were performed, which showed increased very-low-density lipoprotein remnants corresponding to the lipid profile observed in FD patients. However, instead of the expected <em>APOE</em> ε2/ε2 genotype, our patient showed <em>APOE</em> ε3/ε4. The <em>APOE</em> gene was sequenced, revealing a c.509C &gt; A:p. (Ala170Asp) variant (also known as <em>APOE</em> Las Vegas), which has been described once in a patient with lipoprotein glomerulopathy. Lipid-lowering therapy was initiated, which resulted in a slight improvement of renal function and lipid profile. This Dutch case further supports the pathogenicity of the <em>APOE</em> Las Vegas variant and emphasizes the importance of timely diagnosis of lipoprotein glomerulopathy to institute appropriate treatment.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"19 1","pages":"Pages 183-187"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel 327bp Alu element insertion in LDLR exon 17 causes alternative splicing and familial hypercholesterolemia","authors":"Mohamed Imran PhD ,&nbsp;Divya Agarwal DM ,&nbsp;Kriti Menon B.Tech ,&nbsp;Vinod Scaria PhD ,&nbsp;Sridhar Sivasubbu PhD","doi":"10.1016/j.jacl.2024.11.006","DOIUrl":"10.1016/j.jacl.2024.11.006","url":null,"abstract":"<div><h3>BACKGROUND</h3><div>Homozygous familial hypercholesterolemia (HoFH) is a severe form of familial hypercholesterolemia (FH) characterized by high low-density lipoprotein cholesterol (LDL-C) levels and increased coronary artery disease risk. This study reports a novel Alu insertion in the <em>LDLR</em> gene in a consanguineous Indian family, causing FH.</div></div><div><h3>OBJECTIVE</h3><div>To identify and characterize the mutation causing HoFH in a proband and their family members.</div></div><div><h3>METHODS</h3><div>Clinical exome sequencing was conducted on the proband with subsequent bioinformatic analysis of single nucleotide variants, loss-of-function variants, structural variants, and mobile element insertions (MEI). Polymerase chain reaction (PCR) amplification and Sanger sequencing of exon 17 of the <em>LDLR</em> gene were performed to elucidate the sequence and length of the Alu insertion. Additionally, RNA analysis of the proband identified splice site events.</div></div><div><h3>RESULTS</h3><div>Bioinformatic analysis revealed a small sequence duplication followed by an Alu element insertion. PCR amplification and Sanger sequencing uncovered a 17 base pair (bp) duplication at the breakpoint, a “T” base insertion, followed by a 309 bp Alu Yb8 insertion. This led to a 70 bp deletion at the beginning of exon 17 due to alternative splicing, resulting in a frameshift and extended protein truncation. The proband and siblings were homozygous for the mutation, while the parents and 2 other family members were heterozygous.</div></div><div><h3>CONCLUSION</h3><div>Our study uncovers a novel AluYb8 element insertion in the <em>LDLR</em> gene, highlighting the need for MEI detection in genetic screening for FH. Reanalyzing FH cohorts for MEIs could significantly improve diagnostic accuracy and enhance our understanding of FH genetics.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"19 1","pages":"Pages 114-124"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023641","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":"In memoriam: A tribute to Dr Scott M. Grundy","authors":"Neil J. Stone MD,&nbsp;Roger S. Blumenthal MD,&nbsp;William Virgil Brown MD,&nbsp;Ada Cuevas MD,&nbsp;Antonio M. Gotto Jr. MD, D.Phil,&nbsp;Carl E. Orringer MD,&nbsp;Sidney C. Smith Jr. MD,&nbsp;Gloria L. Vega PhD","doi":"10.1016/j.jacl.2025.02.006","DOIUrl":"10.1016/j.jacl.2025.02.006","url":null,"abstract":"","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"19 1","pages":"Pages 3-6"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143592303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of a homozygous variant in ABCG5 by panel sequencing in a Pakistani family with sitosterolemia: Genotype-phenotype correlation and management considerations","authors":"Wajahat Bin Naeem M.Phil ,&nbsp;Mehreen Ali Khan FCPS ,&nbsp;Zaineb Akram PhD ,&nbsp;Tehseen Ullah Khan Afridi M.Phil ,&nbsp;Tariq Azam Khattak FCPS ,&nbsp;Muhammad Asghar Khan PhD ,&nbsp;Muhammad Yousaf FCPS ,&nbsp;Humayoon Shafique Satti PhD","doi":"10.1016/j.jacl.2024.09.012","DOIUrl":"10.1016/j.jacl.2024.09.012","url":null,"abstract":"<div><div>Sitosterolemia is a rare autosomal recessive disorder characterized by impaired excretion of plant sterols, leading to their accumulation in tissues and organs. We identified a hitherto unreported homozygous variant, in ATP-binding cassette sub-family G member 5 (<em>ABCG5</em>) (NM_022436.3) c.274A &gt; <em>G</em> p.(Lys92Glu), segregating in two affected siblings (Sit1C and Sit1F) of a consanguineous Pakistani family, during genetic workup for hereditary hemolytic anemia. Both patients had anemia, history of gum bleeding and easy bruising. Peripheral film revealed stomatocytes and macrothrombocytopenia. Plasma sitosterol level was found to be significantly high (27.7 mg/dL and 25.1 mg/dL for Sit1C and F, respectively), confirming diagnosis of sitosterolemia in both patients. Treatment with ezetimibe, a sterol absorption inhibitor, resulted in significant decrease in sitosterol as well as low-density lipoprotein-cholesterol, in these patients. This study confirms the potential of panel sequencing as a diagnostic tool for sitosterolemia. Definitive diagnosis has significant clinical implications for genetic counseling and management strategies, such as dietary modifications and successful management with ezetimibe.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"19 1","pages":"Pages 156-161"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621425","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":"Novel pathogenic variant in the LCAT gene in a compound heterozygous patient with fish-eye disease and a mild phenotype","authors":"Masaaki Miyata MD, PhD ,&nbsp;Masayuki Kuroda PhD ,&nbsp;Junko Miyoshi MS ,&nbsp;Mika Kirinashizawa BS ,&nbsp;Rora Nagasawa MS ,&nbsp;Misato Yamamoto MS ,&nbsp;Yuichi Akasaki MD, PhD ,&nbsp;Kensuke Utatsu MD, PhD ,&nbsp;Yoshiro Maezawa MD, PhD ,&nbsp;Koutaro Yokote MD, PhD ,&nbsp;Mitsuru Ohishi MD, PhD","doi":"10.1016/j.jacl.2024.09.013","DOIUrl":"10.1016/j.jacl.2024.09.013","url":null,"abstract":"<div><h3>BACKGROUND AND OBJECTIVE</h3><div>Low high-density lipoprotein (HDL)-cholesterol and corneal opacity are associated with fish-eye disease (FED), familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD), apolipoprotein AI deficiency, and Tangier disease. The differential diagnosis is made by clinical and biochemical tests. Measuring the LCAT activity is the ideal way to distinguish conditions caused by <em>LCAT</em> gene variants (FED and FLD) from the other 2 diseases. However, this is not accessible from all clinics. The cholesteryl ester/total cholesterol (CE/TC) ratio, which is below the reference range in most cases with <em>LCAT</em> gene variants, has been proposed as an alternative. We report a case of compound heterozygous FED with a CE/TC ratio within the reference range.</div></div><div><h3>METHODS</h3><div>LCAT activity assays and genetic analyses were performed using patients’ blood samples. Identified <em>LCAT</em> gene variants were examined by an <em>in vitro</em> expression assay.</div></div><div><h3>RESULTS</h3><div>The proband showed approximately 20% LCAT α-activity relative to the normolipidemic controls, whereas a patient with a typical FED-causing variant (p.Thr147Ile) showed only 3% activity. We identified compound heterozygous variants (c.101C &gt; T/c.460A &gt; <em>G</em>) resulting in a p.Pro34Leu/p.Asn154Asp amino acid residue substitution in the <em>LCAT</em> gene of the proband. The former variant has been reported previously, but the latter was newly identified. An <em>in vitro</em> expression assay demonstrated that the LCAT α-activity of the p.Asn154Asp variant significantly decreased regarding the wild type, but it was relatively well preserved compared to the typical FED-causing variants (p.Pro34Leu and p.Thr147Ile).</div></div><div><h3>CONCLUSION</h3><div>These results suggest that the residual 20% LCAT α-activity is sufficient to normalize CE/TC, but not sufficient to prevent the development of corneal opacity in FED.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"19 1","pages":"Pages 125-133"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Falsely elevated triglyceride and lipase levels due to hyperglycerolemia in a burn patient treated with topical silver sulfadiazine","authors":"Chutintorn Sriphrapradang MD ,&nbsp;Pornpen Srisawasdi PhD ,&nbsp;Prapimporn Chattranukulchai Shantavasinkul MD ,&nbsp;Saranya Auparakkitanon PhD ,&nbsp;Jatupon Krongvorakul MD ,&nbsp;Suweejuk Punprasit BSc ,&nbsp;Supasuta Wongdama MD","doi":"10.1016/j.jacl.2024.10.006","DOIUrl":"10.1016/j.jacl.2024.10.006","url":null,"abstract":"<div><div>Pseudohypertriglyceridemia is an overestimation of serum triglyceride levels, potentially leading to an inaccurate diagnosis of hypertriglyceridemia. This can result from hyperglycerolemia, which interferes with enzymatic measurement methods. Hyperglycerolemia may arise from drugs or genetic glycerol kinase defects. We present a case of a severely burned patient with very high triglyceride levels (up to 5696 mg/dL) that was resistant to lipid-lowering treatment, identified during the work up for pancreatitis associated with elevated lipase levels. Despite the very high triglyceride levels reported in the laboratory results, the standing plasma showed clear plasma, with no significant peak of pre-beta lipoprotein observed on serum lipoprotein electrophoresis. Serum apolipoprotein B levels were low, and urine triglyceride levels were high. This case confirms that very high serum glycerol levels caused the false elevations of triglyceride and lipase levels, resulting from hyperglycerolemia induced by the massive topical application of silver sulfadiazine cream (containing glycerine and glyceryl stearate) to the severely burned wound, which interfered with the laboratory assays. Triglyceride and lipase levels dramatically decreased after reducing the dose of silver sulfadiazine cream. No genetic defects related to glycerol kinase deficiency were identified.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"19 1","pages":"Pages 162-166"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716224","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":"Lipoprotein(a) levels in a population with clinical atherosclerotic cardiovascular disease in the United States: A subanalysis from the Lp(a)HERITAGE study","authors":"Michael D. Shapiro DO, MCR ,&nbsp;Tariq M. Haddad MD ,&nbsp;Howard S. Weintraub MD ,&nbsp;Seth J. Baum MD ,&nbsp;Khaled Abdul-Nour MD ,&nbsp;Samiha Sarwat PhD ,&nbsp;Vadim Paluy MD ,&nbsp;Wess Boatwright PharmD, MBA ,&nbsp;Auris Browne MD ,&nbsp;Imran Ayaz MD ,&nbsp;Cheryl A. Abbas PharmD ,&nbsp;Christie M. Ballantyne MD","doi":"10.1016/j.jacl.2024.11.007","DOIUrl":"10.1016/j.jacl.2024.11.007","url":null,"abstract":"<div><h3>BACKGROUND</h3><div>Elevated lipoprotein(a) (Lp[a]) is the most common inherited dyslipidemia that is independently and causally associated with increased atherosclerotic cardiovascular disease (ASCVD) risk. However, data from diverse populations with ASCVD are lacking.</div></div><div><h3>OBJECTIVE</h3><div>To evaluate Lp(a) levels in a diverse, contemporary United States (US) population with ASCVD, stratified by race, ethnicity, and sex.</div></div><div><h3>METHODS</h3><div>Lp(a)HERITAGE (NCT03887520) was a multicenter study that estimated the prevalence of elevated Lp(a) in adults (18–80 years) with ASCVD. US participants with Lp(a) measured in nmol/L pre- or post-enrollment were included in this subanalysis. This study was descriptive; therefore, no statistical comparisons were made.</div></div><div><h3>RESULTS</h3><div>Of all US participants, 14% had an Lp(a) measurement pre-enrollment. This subanalysis included 7679 US participants with Lp(a) measurements in nmol/L (80.5% White; 66.4% male; mean age 63.8 years [standard deviation ± 9.7]). Median Lp(a) was &gt; 2.5-fold higher in Black participants (132.0 nmol/L; IQR, 57.1–239.6) vs the overall population (52.1 nmol/L; IQR, 15.7–167.8), and higher in females compared with males (69.4 nmol/L; IQR, 20.1–194.7 vs 45.6 nmol/L; IQR, 14.0–152.6, respectively). Lp(a) levels ≥ 125 nmol/L were more prevalent among Black (52.0%) and female (38.9%) participants vs the overall population (33.3%).</div></div><div><h3>CONCLUSION</h3><div>In US Lp(a)HERITAGE participants, only 14% had an Lp(a) measurement pre-enrollment, despite having ASCVD. One-third of participants demonstrated Lp(a) levels ≥ 125 nmol/L, the threshold for high ASCVD risk, which was higher among Black (1/2) and female (2/5) participants, suggesting a greater need for Lp(a) testing in these groups to inform ASCVD risk mitigation.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"19 1","pages":"Pages 28-38"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complex dyslipidemia induced by lorlatinib therapy: A case study","authors":"Julianna West MD ,&nbsp;Abhimanyu Garg MD","doi":"10.1016/j.jacl.2024.10.003","DOIUrl":"10.1016/j.jacl.2024.10.003","url":null,"abstract":"<div><h3>CONTEXT</h3><div>Lorlatinib is an anaplastic lymphoma kinase (ALK) inhibitor, which is currently used for the treatment of <em>ALK</em>-positive metastatic non-small cell lung cancer (NSCLC). Previous reports have noticed an association between lorlatinib and hyperlipidemia, however the specific mechanisms for this side effect remain unknown. Some investigators have reported nephrotic syndrome to be the underlying cause of lorlatinib-induced hyperlipidemia.</div></div><div><h3>CASE REPORT</h3><div>A 59-year-old female with NSCLC presented with marked elevation of lipid levels, including total cholesterol, triglycerides, low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol (HDL-C), after initiation of lorlatinib therapy. Despite high dose atorvastatin and ezetimibe, lipid levels remained elevated. A 24-hour urine collection revealed only 226 mg of protein excretion.</div></div><div><h3>CONCLUSIONS</h3><div>Lorlatinib induced a complex dyslipidemia in our patient with elevations of both LDL-C and HDL-C. The underlying mechanism of lorlatinib-induced hyperlipidemia remains unknown and is unlikely to be secondary to nephrotic syndrome in many patients.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"19 1","pages":"Pages 178-182"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621420","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":"Variance in the composition and number of VLDL and LDL particles with increasing triglyceride or increasing ApoB concentrations","authors":"Justine Cole MBChB, MMed ,&nbsp;Patrick Couture MD, PhD ,&nbsp;André J. Tremblay PhD ,&nbsp;Allan D. Sniderman MD","doi":"10.1016/j.jacl.2024.09.009","DOIUrl":"10.1016/j.jacl.2024.09.009","url":null,"abstract":"<div><h3>OBJECTIVE</h3><div>The importance of any enhanced atherogenicity of triglyceride (TG)-rich lipoproteins (TRLs) will depend on the relative abundance of these particles compared with low-density lipoprotein (LDL) or total apolipoprotein (apo)B. Accordingly, we determined the contribution that TRLs make to total apoB as TG or apoB concentrations increase. We also describe compositional changes in TRLs as TG or apoB increases to assess whether very low-density lipoprotein (VLDL-[C]) is a valid proxy for VLDL-apoB.</div></div><div><h3>METHODS</h3><div>We used sequential ultracentrifugation to separate lipoprotein fractions in plasma samples from 1940 dyslipidemic patients not on lipid-lowering medication, and measured apoB, cholesterol and TG in the plasma and in each subfraction. We analyzed these data in quartiles of TG or apoB.</div></div><div><h3>RESULTS</h3><div>There was wide variance in all parameters in all quartiles of both TG and apoB. Although VLDL-apoB accounted for almost all the increase in total apoB across TG quartiles, LDL-apoB still accounted for 80% of the total in TG quartile 4. In contrast, LDL-apoB accounted for 90% of the increase in apoB across apoB quartiles. As TG increases, the increase in VLDL-C is explained more by increased VLDL-C/apoB when TG is moderately elevated, and more by increased VLDL-apoB when TG is very high.</div></div><div><h3>CONCLUSIONS</h3><div>In conclusion, VLDL-apoB only becomes a substantial component of total apoB with extreme hypertriglyceridemia and VLDL-C is not an appropriate proxy for VLDL-apoB.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"19 1","pages":"Pages 72-82"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of plasma phytosterols in sitosterolemia, their kindreds and hyperlipidemia subjects","authors":"Xuanru Ren BS ,&nbsp;Jun Zhang MD ,&nbsp;Luya Wang BS ,&nbsp;Yuxuan Zhang BS ,&nbsp;Jialu Li BS ,&nbsp;Hao Yu BS ,&nbsp;Zhaohai Zheng BS ,&nbsp;Yiqing Zhang BS ,&nbsp;Hesong Zeng MD ,&nbsp;Yan Chen MD ,&nbsp;Junfang Wu PhD","doi":"10.1016/j.jacl.2024.09.002","DOIUrl":"10.1016/j.jacl.2024.09.002","url":null,"abstract":"<div><h3>BACKGROUND</h3><div>Patients suffering from sitosterolemia with <em>ABCG5/8</em> mutation typically present with early-onset or rapidly progressive atherosclerosis. Their kindreds with partial genetic deficiencies of ABCG5/8 are often considered healthy. However, discerning sitosterolemia from its familial kindreds and hyperlipidemia subjects has remained challenging.</div></div><div><h3>METHODS</h3><div>Here we retrospectively recruited 7 families including 8 individuals diagnosed with sitosterolemia subjects, and 14 kindreds carrying single gene mutations. Additionally, 17 individuals with hyperlipidemia and 130 healthy controls served as positive and negative controls, respectively. A total of 6 phytosterols combined with cholesterol absorption indices (including sitosterol, campesterol, stigmasterol, and cholestanol) and cholesterol synthesis markers (desmosterol and 7-dehydrocholesterol), was compared across the aforementioned 4 groups.</div></div><div><h3>RESULTS</h3><div>As expected, the sitosterolemia subjects with double mutations demonstrated significantly elevated levels of sitosterol and other cholesterol absorption indices. Meanwhile, sitosterolemia kindreds with single gene mutation showed a similar pattern of activated cholesterol-absorption ability to the hyperlipidemia group, but not as high as the double mutation group. Notably, the cholesterol-synthesis enzyme 7-dehydrocholesterol reductase displayed an increase in the hyperlipidemia group but a decrease in the sitosterolemia kindred group, suggesting a potential discriminative role of 7-dehydrocholesterol in distinguishing between these 2 groups. The combination of phytosterols was more valuable than clinical lipid index for sitosterolemia diagnosis.</div></div><div><h3>CONCLUSION</h3><div>Our study revealed mild disruptions of cholesterol absorption capacities in sitosterolemia kindreds with single mutations. Furthermore, the combination of 6 phytosterols proved effective in distinguishing between sitosterolemia, its single mutation carriers, and hyperlipidemia patients.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"19 1","pages":"Pages 146-155"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}