CETP deficiency due to a novel mutation in the CETP gene promoter and its effect on cholesterol efflux and selective uptake into hepatocytes

Plengpanich, Wanee; Goff, Wilfried Le; Poolsuk, Suchanya; Julia, Zélie; Guérin, Maryse; Khovidhunkit, Weerapan

doi:10.1016/j.atherosclerosis.2011.01.051

Cited by 25 publications

(15 citation statements)

References 16 publications

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“…Many CETP gene mutations are reported, such as nonsense mutations (n=8), splice junction mutations (n=6), missense mutations (n=5), small gene deletions and insertions (n=4), promoter mutations (n=2) and others (n=1) (Fig.6) [8,9,20,[27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46]. In the present study, we identified c.653_654delGGinsAAAC and c.658G>A from several subjects with HALP, and it suggests that nonsense and splicing defect mutations account for the majority of CETP gene mutations.…”

Section: Discussionmentioning

confidence: 99%

Novel mutations of cholesteryl ester transfer protein (CETP) gene in Japanese hyperalphalipoproteinemic subjects

Ohtani

Inazu

Noji

et al. 2012

Clinica Chimica Acta

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Background: The half of hyperalphalipoproteinemia (HALP) in Japan is caused by CETP gene mutations. Other than two prevalent mutations (D442G and Intron 14 splicing donor site +1 G>A), some rare CETP mutations are found in Japanese HALP subjects.Methods: CETP gene analysis of genomic DNA from subjects was performed by restriction fragment length polymorphism (RFLP) and sequencing analysis. Mutations which were suspected to cause a splicing defect or a protein secretion defect were investigated in COS-1 cells transfected with a CETP minigene construct or a cDNA expression vector.Results: Each of three subjects was identified as a carrier of CETP gene mutation of a compound heterozygote of c.653_654delGGinsAAAC and Intron 14 splicing donor site +1 G>A, a heterozygote of c.658G>A or a homozygote of L261R. The c.658G>A mutation was located at the last nucleotide of exon 7, and it was confirmed to cause splicing abnormality revealed by the CETP minigene analysis. The L261R CETP was not secreted to conditioned media of the cells.Conclusions: Three novel CETP gene mutations are responsible for HALP by CETP deficiency. It is predicted that there are more rare CETP gene mutations in Japanese, and these multiple rare mutations alone or a combination with each of prevalent mutations responsible for mild-to-moderate or marked HALP, respectively.3

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Section: Discussionmentioning

confidence: 99%

Novel mutations of cholesteryl ester transfer protein (CETP) gene in Japanese hyperalphalipoproteinemic subjects

Ohtani

Inazu

Noji

et al. 2012

Clinica Chimica Acta

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“…HDL particles from subjects with complete CETP deficiency have an abnormal size and exhibit relevant changes in the apoprotein content [38], and their functionality is a matter of debate. HDL2 from subjects with CETP mutations more efficiently promoted cholesterol efflux compared to control HDL2 [39,40,41]. A case of complete CETP deficiency resulted in extremely elevated HDL-C and apoA-I levels, with a significant increase in both LpA-I and LpA-I:A-II levels, a high pre-β-particle content and HDL2 larger than normal [42].…”

Section: Effects Of Genetics On Hdl Subpopulationsmentioning

confidence: 99%

High-Density Lipoprotein Subfractions - What the Clinicians Need to Know

2013

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Although the inverse relationship between plasma levels of high-density lipoprotein (HDL) and cardiovascular disease has been largely demonstrated, many observations have suggested that the assessment of HDL functionality might be more informative than a simple measurement of HDL-cholesterol plasma levels. HDLs are a class of structurally and functionally heterogeneous particles; in atherosclerosis-related diseases, changes in HDL subfraction levels and functions are frequently observed. Circulating levels of large HDL particles are decreased in dyslipidaemic conditions, while levels of small dense HDL particles are increased in patients with coronary heart disease. Furthermore, specific genetic defects in proteins involved in HDL metabolism significantly impact the distribution of HDL subpopulations. Finally, many drugs used for dyslipidaemia induce changes in HDL subfractions strictly related to cardiovascular disease. Although several methods exist to evaluate HDL subclass levels, most of them are not easily applicable in clinical practice, due to the costs and high variability. However, the possibility to measure the levels of specific HDL subfractions in patients with atherosclerosis-related diseases might help to better define their cardiovascular risk.

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“…Gene CETP codes for cholesterol ester transfer protein; in its promoter, it contains a known biomedical SNP marker: deletion of the region G −72 GGCGGACATACATATAC −54 (18 bp long) at position -54 relative to the transcription start site (hereafter: -54[18 bp]DEL); this is a marker of hyperalphalipoproteinemia that lowers the risk of atherosclerosis [77, 78]. A keyword search uncovered clinical data on circadian pathogenesis (postprandial flare-up) of this disorder in diabetes [79].…”

Section: Resultsmentioning

confidence: 99%

“…A keyword search uncovered clinical data on circadian pathogenesis (postprandial flare-up) of this disorder in diabetes [79]. Near this known SNP marker, we found three unannotated SNPs (rs17231520, rs757176551, and rs569033466), which can increase CETP expression (Table 1) and thereby increase the risk of atherosclerosis [77–79] and of hypoalphalipoproteinemia which causes hepatic chronopathologies [80]. …”

Section: Resultsmentioning

confidence: 99%

Candidate SNP Markers of Chronopathologies Are Predicted by a Significant Change in the Affinity of TATA-Binding Protein for Human Gene Promoters

Пономаренко

Рассказов

Суслов

et al. 2016

BioMed Research International

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Variations in human genome (e.g., single nucleotide polymorphisms, SNPs) may be associated with hereditary diseases, their complications, comorbidities, and drug responses. Using Web service SNP_TATA_Comparator presented in our previous paper, here we analyzed immediate surroundings of known SNP markers of diseases and identified several candidate SNP markers that can significantly change the affinity of TATA-binding protein for human gene promoters, with circadian consequences. For example, rs572527200 may be related to asthma, where symptoms are circadian (worse at night), and rs367732974 may be associated with heart attacks that are characterized by a circadian preference (early morning). By the same method, we analyzed the 90 bp proximal promoter region of each protein-coding transcript of each human gene of the circadian clock core. This analysis yielded 53 candidate SNP markers, such as rs181985043 (susceptibility to acute Q fever in male patients), rs192518038 (higher risk of a heart attack in patients with diabetes), and rs374778785 (emphysema and lung cancer in smokers). If they are properly validated according to clinical standards, these candidate SNP markers may turn out to be useful for physicians (to select optimal treatment for each patient) and for the general population (to choose a lifestyle preventing possible circadian complications of diseases).

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CETP deficiency due to a novel mutation in the CETP gene promoter and its effect on cholesterol efflux and selective uptake into hepatocytes

Cited by 25 publications

References 16 publications

Novel mutations of cholesteryl ester transfer protein (CETP) gene in Japanese hyperalphalipoproteinemic subjects

Novel mutations of cholesteryl ester transfer protein (CETP) gene in Japanese hyperalphalipoproteinemic subjects

High-Density Lipoprotein Subfractions - What the Clinicians Need to Know

Candidate SNP Markers of Chronopathologies Are Predicted by a Significant Change in the Affinity of TATA-Binding Protein for Human Gene Promoters

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