Genetic determinants of HDL: monogenic disorders and contributions to variation

Klos, Kathy L.E.; Kullo, Iftikhar J.

doi:10.1097/hco.0b013e3281a8acad

Cited by 40 publications

(42 citation statements)

References 89 publications

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“…The most common genetic disorder of HDL-C is familial hypoalphalipoproteinemia (FHA), defi ned as HDL-C levels below the 10th percentile for age and gender (HDL-C levels between 20 and 40 mg/dl) and a family history of low HDL-C levels in at least one fi rst-degree relative ( 20,29 ). FHA is a common fi nding in patients with premature CAD ( 2,30 ).…”

Section: Remodeling Of Hdlmentioning

confidence: 99%

Genetic causes of high and low serum HDL-cholesterol

Weissglas‐Volkov

Pajukanta

2010

Journal of Lipid Research

180

132

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Section: Remodeling Of Hdlmentioning

confidence: 99%

Genetic causes of high and low serum HDL-cholesterol

Weissglas‐Volkov

Pajukanta

2010

Journal of Lipid Research

180

132

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“…In the presence of cofactor, APOA-I (see Section 2.3), lecithin-cholesteryl acyltransferase (LCAT), catalyzes the esterification of free cholesterol and, can metabolize larger HDL-C particles to smaller HDL-C particles (Klos and Kullo, 2007;Miller and Zhan, 2004). The human LCAT is located on chromosome 16 (16q22.1).…”

Section: Genetic Variation In Enzymes Involved In Lipid Metabolism Anmentioning

confidence: 99%

“…Although complete loss of CETP function is rare and can yield HDL-C levels up to five times higher than normal (Klos and Kullo, 2007), three common polymorphisms (Table 1: TaqIB (rs708272); -629C>A (rs1800775); Ile405Val (rs5882)) can all modestly inhibit CETP activity and have been consistently associated with higher HDL-C levels (Bernstein et al, 2003;Blankenberg et al, 2004;Boekholdt et al, 2005;Boekholdt and Thompson, 2003;Borggreve et al, 2005;Eiriksdottir et al, 2001;Freeman et al, 2003;Kathiresan et al, 2008a;Klerkx et al, 2003;Tai et al, 2003b;Thompson et al, 2008). The CETP gene is located on chromosome 16 (16q21).…”

Section: Genetic Variation In Enzymes Involved In Lipid Metabolism Anmentioning

confidence: 99%

“…The human LPL gene is located on chromosome 8 (8p22). Several LPL SNPs have been associated with HDL-C (Table 1) (Ahn et al, 1993;Corella et al, 2002;Holmer et al, 2000;Klos and Kullo, 2007;Klos et al, 2006;Komurcu-Bayrak et al, 2007;Lee et al, 2004;Nettleton et al, 2007;Senti et al, 2001;Wittrup et al, 1999); however, many of them are in strong linkage disequilibrium with each other (e.g., rs320, rs326, rs13702, rs10105606) (Boes et al, 2009;Heid et al, 2008). Hepatic lipase (HL; LIPC) is a glycoprotein that is synthesized by liver cells (hepatocytes) and catalyzes the hydrolysis of TG and phospholipids (Miller et al, 2003).…”

Section: Genetic Variation In Enzymes Involved In Lipid Metabolism Anmentioning

confidence: 99%

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Dyslipidemia: Genetics and Role in the Metabolic Syndrome

Nock¹,

Pillai²

2012

Dyslipidemia - From Prevention to Treatment

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“…Mutações no ABCA1 também podem resultar em Hipoalfalipoproteinemia Familial que é caracterizada por baixas concentrações plasmáticas de HDL-C e ausência das manifestações clínicas da doença de Tangier (KLOS; KULLO, 2007).…”

Section: Hdl E O Transporte Reverso Do Colesterolunclassified

Efeito de hipolipemiantes sobre a expressão de genes envolvidos no transporte reverso do colesterol

Genvigir¹

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The efficacy of statins in reducing the risk of coronary events is not completely explained by their effects in decreasing cholesterol low-density lipoprotein (LDL-C). One of their additional effects may result from the change in concentration of highdensity lipoprotein (HDL), recognized as atheroprotective, mainly for the role in reverse cholesterol transport (RCT). The membrane transporters, as ATP-binding cassette, ABCA1 and ABCG1, and scavenger receptor BI (SRBI) are important proteins involved in the RCT and their genes are regulated by various transcription factors, including the liver-X-receptors (LXRs) . In order to evaluate the effects of lipid lowering on expression of ABC transporters and SRBI receptor, the mRNA expression of ABCA1, ABCG1, SCARB1, NR1H3 (LXRα) and NR1H2 (LRXβ) was assessed by real time PCR in HepG2 (hepatic origin) and Caco-2 (intestinal origin) cells treated with atorvastatin or simvastatin (10 µM) and/or ezetimibe (up to 5 µM) for 24 hours. Furthermore, the expression of these genes was evaluated in peripheral blood mononuclear cells (PBMC) of 50 normolipidemic (NL) and 71 hypercholesterolemic (HC) patients treated with atorvastatin (10mg/d/4 weeks, n = 48) or simvastatin and/or ezetimibe (10mg/d/4 or 8 weeks, n = 23). The possible association between ABCA1 C-14T and R219K polymorphisms and mRNA expression in PBMC was also evaluated by PCR-RFLP. SCARB1 was the most expressed in HepG2 and Caco-2 cells, followed by NR1H2, NR1H3, ABCG1 and ABCA1 in HepG2 or by ABCG1 and ABCA1 in Caco-2. The treatment with statins (1 or 10 µM) or ezetimibe (5 µM) for 12 or 24 hours, increased mRNA expression of ABCG1 but not ABCA1 and SCARB1 in HepG2 cells. Moreover, in HepG2 cells, atorvastatin also upregulated NR1H2 and NR1H3 only at 10.0 µM, meanwhile ezetimibe downregulated NR1H2 but did not change NR1H3 expression. In Caco-2 cells, atorvastatin or simvastatin treatment for 12 or 24 hours reduced the amount of ABCA1 transcript and did not alter the ABCG1 and SCARB1 expressions, despite the tendency to decrease ABCG1 mRNA expression after simvastatin treatment (p = 0.07). After treatment with ezetimibe alone (up to 5 µM) no change in mRNA expression was observed in Caco-2 cells; however, after 24 hours-simvastatin and ezetimibe treatments decreased the transcription of ABCA1 and ABCG1, but not of SCARB1. Unlike cell lines, in PBMC, NR1H2 and ABCG1 were the most expressed, followed by SCARB1 and ABCA1 and finally by the NR1H3. HC patients showed higher NR1H2 and NR1H3 basal expressions, but not of other genes, compared to NL (p <0.05). Moreover, in HC individuals, the ABCA1 basal expression was higher in individuals carrying -14T allele of -14C> T polymorphism when compared with -14CC carriers (p = 0.034). Treatment with statins, ezetimibe, or combined therapy downregulated ABCA1 and ABCG1 expression. For SCARB1, NR1H2 and NR1H3, no change in mRNA expression in PBMC was detected after treatments. After all phases of treatment, ABCA1 and ABCG1 as well as NR1H2 and NR1H3 were significantly corre...

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Genetic determinants of HDL: monogenic disorders and contributions to variation

Cited by 40 publications

References 89 publications

Genetic causes of high and low serum HDL-cholesterol

Genetic causes of high and low serum HDL-cholesterol

Dyslipidemia: Genetics and Role in the Metabolic Syndrome

Efeito de hipolipemiantes sobre a expressão de genes envolvidos no transporte reverso do colesterol

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