Lack of correlation between SREBF1 genotype and hyperlipidemia in individuals treated with highly active antiretroviral therapy

Yang, Aiming; King, Martin; Han, Lixin; Isaacson, Jeffrey D.; Mueller, Toby; Grimm, David R.; Scott, Charles; Katz, David A.

doi:10.1097/00002030-200309260-00024

Cited by 12 publications

(7 citation statements)

References 4 publications

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“…More recent studies [23,24] have associated nucleotide variations in resistin and β2 adrenegic receptor ( ARβ2 ) with the occurrence of lipodystrophy. In addition, tumor necrosis factor-α (TNFα) [20,25,26] and nuclear transcription-factor sterol response element-binding protein 1c (SREBP1c) [27,28] have also been shown to affect HIV-induced lipodystrophy, but confirmation is required in long-term prospective studies.…”

Section: Discussionmentioning

confidence: 99%

Antiretroviral treatment-induced dyslipidemia in HIV-infected patients is influenced by the APOC3-related rs10892151 polymorphism

et al. 2011

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BackgroundThe recently observed association between the APOC3-related rs10892151 polymorphism and serum triglyceride levels has prompted us the possibility to explore whether this genetic variant may play a major role in human immunodeficiency virus (HIV)/antiretroviral therapy-induced dyslipidemia.MethodsWe determined the rs10892151 genotype distribution and serum apolipoprotein (apo) C-III concentration in a group of HIV-infected patients (n = 208) and in a group of age and sex-matched healthy volunteers (n = 200). Circulating lipid and lipoprotein levels were followed for 12 months after antiretroviral treatment initiation in the HIV-infected group.ResultsThere were no significant variations in the frequency of the A allele between the healthy and HIV-infected groups (7.5 vs. 8.6%, respectively; p = 0.7); additionally, the A allele was not related to serum apo C-III concentration. However, among patients receiving protease inhibitor (PI) treatment, carriers of the A allele had significantly increased serum triglyceride (5.76 ± 2.54 mmol/L) and total cholesterol (6.63 ± 2.85 mmol/L) concentrations together with depressed levels of HDL-cholesterol (0.75 ± 0.3 mmol/L) when compared with patients not carrying the allele (2.43 ± 1.32, 5.2 ± 2.17 and 1.24 ± 0.4 mmol/L, respectively) at the end of the study. This effect was only evident for HDL-cholesterol concentration when patients were treated with non-nucleoside reverse transcriptase inhibitors (1.05 ± 0.4 vs. 1.28 ± 0.4 mmol/L).ConclusionsThe A allelic variant of the rs10892151 polymorphism is not associated with serum apo C-III concentration, but predisposes HIV-infected patients to less favorable lipid profile, particularly in those patients treated with PIs.

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Section: Discussionmentioning

confidence: 99%

Antiretroviral treatment-induced dyslipidemia in HIV-infected patients is influenced by the APOC3-related rs10892151 polymorphism

et al. 2011

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“…SREBP1c stimulates fatty acid and TG synthesis in the liver and adipose tissue, and promotes adipocyte differentiation, while SREBP2 controls several steps of cholesterol synthesis (11). In a first report (16), this polymorphism has been associated with the magnitude of lipid changes occurring upon PI therapy, but this finding has been contradicted in a larger cohort with a longer follow-up period (17). In mice, administration of ritonavir leads to stimulation of TG and cholesterol synthesis that is correlated with accumulation of mature SREBP1c and SREBP2 within the nucleus in both liver and adipose tissue (11).…”

Section: Sterol Response Element Binding Proteins (Srebp1c)mentioning

confidence: 99%

Impact of genetic polymorphisms on the risk of lipid disorders in patients on anti-HIV therapy

Bonnet

Genoux²,

Bernard³

et al. 2007

Clinical Chemical Laboratory Medicine

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Active anti-HIV therapy can induce hypertriglyceridemia, low high-density lipoprotein (HDL) and insulin resistance, eventually accompanied by clinical lipodystrophy, associated loss of subcutaneous adipose tissue and an increase in abdominal adiposity. The frequency of these metabolic disorders is approximately 50% and host genetic factors might confer particular susceptibility. Variants of apolipoproteins (apo) A5 and C3, interacting with APOE genotypes, have been associated with the severity of antiretroviral therapy-induced dyslipidemia and with occurrence of lipodystrophy, and for APOC3, with objective criteria of fat redistribution. Genetic polymorphisms of the nuclear transcription-factor sterol response element-binding proteins (SREBP1c) and of tumor necrosis factor-alpha (TNFalpha) have yielded contrasting results. Other candidate genes will be explored to define a pharmacogenomic strategy to identify patients at high risk of metabolic disorders upon antiretroviral therapy.

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“…Genetic variants of the SREBP-1 gene, on the other hand, have been associated with insulin resistance, risk for diabetes mellitus ( Laudes et al, 2004 ), obesity ( Eberle et al, 2004a ), atherosclerosis ( Vedie et al, 2001 ), and with elevated total and LDL cholesterol levels ( Laudes et al, 2004 ;Vedie et al, 2001 ) as well as with HIV-related hyperlipoproteinemia ( Miserez et al, 2001 ). However, these associations were refuted by other studies ( Yang et al, 2003 ;Rios et al, 2003 ). We have recently shown that a 54 G / C synonymous SNP in exon 18c (G952G, both alleles encode a glycine moiety) is associated with increased cholesterol synthesis but normal serum cholesterol and triglyceride levels in a Finnish population ( Laaksonen et al, 2006 ).…”

Section: Discussionmentioning

confidence: 89%

SREBP-1c Gene Polymorphism is Associated with Increased Inhibition of Cholesterol-Absorption in Response to Ezetimibe Treatment

Berthold¹,

Laaksonen²,

Lehtimäki³

et al. 2007

Exp Clin Endocrinol Diabetes

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Lack of correlation between SREBF1 genotype and hyperlipidemia in individuals treated with highly active antiretroviral therapy

Cited by 12 publications

References 4 publications

Antiretroviral treatment-induced dyslipidemia in HIV-infected patients is influenced by the APOC3-related rs10892151 polymorphism

Antiretroviral treatment-induced dyslipidemia in HIV-infected patients is influenced by the APOC3-related rs10892151 polymorphism

Impact of genetic polymorphisms on the risk of lipid disorders in patients on anti-HIV therapy

SREBP-1c Gene Polymorphism is Associated with Increased Inhibition of Cholesterol-Absorption in Response to Ezetimibe Treatment

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