Complete and Partial Lecithin:Cholesterol Acyltransferase Deficiency Is Differentially Associated With Atherosclerosis

Oldoni, Federico; Baldassarre, Damiano; Castelnuovo, S.; Ossoli, Alice; Amato, Mauro; Capelleveen, J. van; Hovingh, G. Kees; Groot, Eric de; Bochem, Andrea E.; Simonelli, Sara; Barbieri, Simone; Veglia, Fabrizio; Franceschini, Guido; Kuivenhoven, Jan Albert; Holleboom, Adriaan G.; Calabresi, Laura

doi:10.1161/circulationaha.118.034706

Cited by 64 publications

(39 citation statements)

References 22 publications

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“…They found that low HDL-C was robustly associated with increased ASCVD risk, but genetically decreased HDL-C due to impaired LCAT activity was not (65). Similar observations were reported in a recent head-to-head comparison of FLD- and FED-associated LCAT mutations: FLD mutations were associated with decreased atherosclerosis, while FED mutations were associated with increased atherosclerosis (66). The difference appears to relate to the capacity of LCAT to modulate the cholesteryl ester content of apoB-containing lipoproteins.…”

Section: Discussionsupporting

confidence: 67%

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Genetic and secondary causes of severe HDL deficiency and cardiovascular disease

Geller

Polisecki²,

Diffenderfer³

et al. 2018

Journal of Lipid Research

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Supplementary key words apoA-I • ABCA1 • lecithin:cholesterol acyltransferase • lipoprotein lipase • high density lipoprotein metabolism • reverse cholesterol metabolism • dyslipidemia • genes in lipid disorders It has been concluded that genetic HDL deficiency is not causative for atherosclerotic cardiovascular disease (ASCVD), in contrast to genetic hypercholesterolemia associated with elevated levels of LDL cholesterol (LDL-C) or genetic hypertriglyceridemia (1, 2). This assessment has been reported in high-impact journals by a very large number of authors, representing some of the most prominent and well-known scientists in our field. The data generated stem from a very large number of subjects studied with and without ASCVD. The analyses, however, were based entirely on SNPs, mainly in intronic DNA regions, and excluded the four most important genes that regulate HDL cholesterol (HDL-C) levels: ABCA1, LCAT, APOA1, and LPL. The exclusions were justified by study findings that 1) genetic variations at the ABCA1, LCAT, APOA1, and LPL gene loci also affect TG and/or LDL-C levels and 2) an LIPC variant was not associated with ASCVD (1, 2). In our view this justification is flawed. Our recent review of severe HDL deficiency has documented that patients with HDL-C levels <20 mg/dl in the absence of secondary causes may have premature ASCVD, especially if such patients are homozygous or compound heterozygous for mutations in the APOA1 or ABCA1 genes (3).

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Section: Discussionsupporting

confidence: 67%

“…In FLD this capacity is lost. Overall, the data indicate that FLD causes kidney failure, while FED causes ASCVD (3,66). In our study we did not see an increased ASCVD prevalence in subjects with severe HDL deficiency associated with LCAT mutations.…”

Section: Discussioncontrasting

confidence: 44%

Genetic and secondary causes of severe HDL deficiency and cardiovascular disease

Geller

Polisecki²,

Diffenderfer³

et al. 2018

Journal of Lipid Research

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“…The authors proposed that this discrepancy may be related to the fact that the capacity of LCAT to generate cholesteryl esters on ApoB-containing lipoproteins is lost in complete LCAT deficiency, while it remains unaffected in partial LCAT deficiency. 72 …”

Section: Disorders That Cause Low Hdl-c Levelsmentioning

confidence: 99%

Primary genetic disorders affecting high density lipoprotein (HDL)

Kosmas¹,

Silverio²,

Sourlas³

et al. 2018

DIC

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There is extensive evidence demonstrating that there is a clear inverse correlation between plasma high density lipoprotein cholesterol (HDL-C) concentration and cardiovascular disease (CVD). On the other hand, there is also extensive evidence that HDL functionality plays a very important role in atheroprotection. Thus, genetic disorders altering certain enzymes, lipid transfer proteins, or specific receptors crucial for the metabolism and adequate function of HDL, may positively or negatively affect the HDL-C levels and/or HDL functionality and subsequently either provide protection or predispose to atherosclerotic disease. This review aims to describe certain genetic disorders associated with either low or high plasma HDL-C and discuss their clinical features, associated risk for cardiovascular events, and treatment options.

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“…Corneal opacity is the common presenting feature in both FLD and FED while haemolytic anaemia and renal disease progressing to renal failure are seen only in FLD 34 35. Lipid profile in both FLD and FED shows low HDL-C (<0.2 mmol/L) and apo-A (<0.2 g/L), while LDL-C concentration is relatively low in FLD (2.6 mmol /L) as compared with FED (3.2 mmol/L) 36. Premature CVD is more often seen in FED than in FLD 36.…”

Section: Introductionmentioning

confidence: 98%

“…Lipid profile in both FLD and FED shows low HDL-C (<0.2 mmol/L) and apo-A (<0.2 g/L), while LDL-C concentration is relatively low in FLD (2.6 mmol /L) as compared with FED (3.2 mmol/L) 36. Premature CVD is more often seen in FED than in FLD 36. Management includes monitoring of renal function and corneal opacity.…”

Section: Introductionmentioning

confidence: 99%

Inherited metabolic disorders and dyslipidaemia

Sulaiman

2019

J Clin Pathol

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Monogenic dyslipidaemia is a diverse group of multisystem disorders. Patients may present to various specialities from early childhood to late in adult life, and it usually takes longer before the diagnosis is established. Increased awareness of these disorders among clinicians is imperative for early diagnosis. This best practice review provides an overview of primary dyslipidaemias, highlighting their clinical presentation, relevant biochemical and molecular tests. It also addresses the emerging role of genetics in the early diagnosis and prevention of these disorders.

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Complete and Partial Lecithin:Cholesterol Acyltransferase Deficiency Is Differentially Associated With Atherosclerosis

Cited by 64 publications

References 22 publications

Genetic and secondary causes of severe HDL deficiency and cardiovascular disease

Genetic and secondary causes of severe HDL deficiency and cardiovascular disease

Primary genetic disorders affecting high density lipoprotein (HDL)

Inherited metabolic disorders and dyslipidaemia

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