The MYLIP p.N342S polymorphism is associated with response to lipid-lowering therapy in Brazilian patients with familial hypercholesterolemia

Santos, P. Marques Dos; Morgan, Aline C.; Jannes, Cinthia E.; Santos, Raul D.; Pereira, Alexandre C.

doi:10.1097/fpc.0000000000000089

Cited by 18 publications

(8 citation statements)

References 38 publications

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“…Moreover, for the crucial role of MYLIP and its relationship with the cell adhesion molecules in cancer metastasis, it is a quite new research field and much things still need to be done to reveal the real mystery under them. The recent studies have indicated that the polymorphism site of MYLIP p.N342S is associated with the response to lipid-lowering therapy and might be a pharmacogenetic marker in patients with familial hypercholesterolemia [ 29 ]. Besides, the p.N342S MYLIP polymorphism is also associated with high total cholesterol level and the modulation of MYLIP activity can affect LDL levels through increasing the degradation of LDL receptors.…”

Section: Discussionmentioning

confidence: 99%

miR-19b promotes breast cancer metastasis through targeting MYLIP and its related cell adhesion molecules

Zhao

et al. 2017

Oncotarget

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miR-19b is a key molecule for cancer development, however its crucial roles in breast cancer metastasis are rarely studied right now. In this study, using several bioinformatics databases to predict the downstream targets for miR-19b, we verified that a novel target gene, myosin regulatory light chain interacting protein (MYLIP), could be directly down-regulated by miR-19b through its 3′-UTR region. MYLIP belongs to the cytoskeletal protein clusters and is involved in the regulation of cell movement and migration. We further explored that miR-19b was highly expressed and negatively correlated with MYLIP expression in breast cancer patient samples from the TCGA database. And the over-expression of miR-19b or inhibition of MYLIP facilitated the migration and metastasis of breast cancer cells, through conducting the wound healing assay and transwell invasion assay. Additionally, miR-19b could obviously promote breast tumor growth in mouse models and affect the expressions of cell adhesion molecules (including E-Cadherin, ICAM-1 and Integrin β1) by down-regulating E-Cadherin expression and up-regulating ICAM-1 and Integrin β1 expressions in vitro and in vivo. Meanwhile, miR-19b effectively activated the Integrin β downstream signaling pathways (such as the Ras-MAPK pathway and the PI3K-AKT pathway) and elevated the expression levels of essential genes in these two pathways. Taken together, these findings comprehensively illustrate the regulatory mechanisms ofmiR-19b in breast cancer metastasis, and provide us new insights for exploring MYLIP and its related cell adhesion molecules as promising therapeutic targets to interfere breast cancer development.

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Section: Discussionmentioning

confidence: 99%

miR-19b promotes breast cancer metastasis through targeting MYLIP and its related cell adhesion molecules

Zhao

et al. 2017

Oncotarget

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“…Another study in a Dutch population showed that there was no difference in IDOL gene rs9370867 polymorphism between two populations with low levels of low-density lipoprotein-cholesterol (LDL-C) and high levels of LDL-C [ 15 ]. Nevertheless, an investigation in a Brazilian population showed that there were no associations between the IDOL gene rs9370867 SNP and lipid profiles [ 16 ]. Furthermore, the relevance of CAD and human IDOL gene remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Genetic polymorphism of IDOL gene was associated with the susceptibility of coronary artery disease in Han population in Xinjiang, China

et al. 2021

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Background Coronary artery disease (CAD) is the leading cause of death worldwide. In this study, we aimed to explore whether some genetic variants of the human IDOL gene were associated with CAD among Chinese population in Xinjiang. Methods We designed two independent case–control studies. The first one included in the Han population (448 CAD patients and 343 controls), and the second one is the Uygur population (304 CAD patients and 318 controls). We genotyped three SNPs (rs2072783, rs2205796, and rs909562) of the IDOL gene. Results Our results revealed that, in the Han female subjects, for rs2205796, the distribution of alleles, dominant model (TT vs. GG + GT) and the additive model (GG + TT vs. GT) showed significant differences between CAD patients and the control subjects (P = 0.048, P = 0.014, and P = 0.032, respectively). Conclusions The rs2205796 polymorphism of the IDOL gene is associated with CAD in the Chinese Han female population in Xinjiang, China.

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“…These data obtained in primary cells further limit, also at the molecular levels, the impact of the rs9370867 variant on the IDOL gene. Of note, patients with familial hypercholesterolaemia, when stratified according to the rs9370867 variant, had similar baseline plasma lipid levels but presented a different magnitude of LDL-C reduction following statin therapy, suggesting that a pharmacogenetic effect for this IDOL SNP could exist [ 29 ]. A similar finding was observed for another IDOL SNP (Rs6924995) in patients treated with rosuvastatin [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

IDOL N342S Variant, Atherosclerosis Progression and Cardiovascular Disorders in the Italian General Population

et al. 2015

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Inducible degrader of the low density lipoprotein receptor (IDOL), is an E3 ubiquitin ligase that negatively modulates low density lipoprotein receptor (LDL-R) expression. Genome-wide association studies (GWAS) indicated that genetic variants in IDOL gene contributes to variation in LDL-C plasma levels and the detailed analysis of a specific locus resulted in the identification of the functional common single nucleotide polymorphism (SNP) rs9370867 (c.G1025A, p.N342S) associates with increased LDL-R degradation and increased LDL-C levels. These findings, however, were not confirmed in two other independent cohorts and no data about the impact of this variant on atherosclerosis progression and cardiovascular risk are available. Aim of this study was to investigate the association between a functional variant in IDOL and atherosclerosis progression in an Italian general population. 1384 subjects enrolled in the PLIC study (Progression of Lesions in the Intima of Carotid) were genotyped by Q-PCR allelic discrimination and the association with anthropometric parameters, plasma lipids and the carotid intima media thickness (cIMT) and the impact on cardiovascular disease (CVD) incidence were investigated. The N342S variant was not associated with changes of the plasma lipid profile among GG, AG or AA carriers, including total cholesterol (249±21, 249±19 and 248±21 mg/dl respectively), LDL-C (158±25, 161±22 and 160±23 mg/dL), cIMT (0.74±0.14, 0.75±0.17 and 0.77±0.15 mm) and CVD incidence. In agreement, the expression of LDLR and the uptake of LDL was similar in macrophages derived from GG and AA carriers. Taken together our findings indicate that the N342S variant does not impact plasma lipid profile and is not associated with atherosclerosis progression and CVD in the general population, suggesting that other variants in the IDOL gene might be functionally linked with cholesterol metabolism.

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The MYLIP p.N342S polymorphism is associated with response to lipid-lowering therapy in Brazilian patients with familial hypercholesterolemia

Abstract: Supplemental Digital Content is available in the text.

Cited by 18 publications

References 38 publications

miR-19b promotes breast cancer metastasis through targeting MYLIP and its related cell adhesion molecules

miR-19b promotes breast cancer metastasis through targeting MYLIP and its related cell adhesion molecules

Genetic polymorphism of IDOL gene was associated with the susceptibility of coronary artery disease in Han population in Xinjiang, China

IDOL N342S Variant, Atherosclerosis Progression and Cardiovascular Disorders in the Italian General Population

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