LDLR and PCSK9 3´UTR variants and their putative effects on microRNA molecular interactions in familial hypercholesterolemia: a computational approach

de Freitas, Renata Caroline Costa; Bortolin, Raul Hernandes; Borges, Jessica Bassani; de Oliveira, Victor Fernandes; Dagli-Hernandez, Carolina; Marçal, Elisangela da Silva Rodrigues; Bastos, Gisele Medeiros; Gonçalves, Rodrigo Marques; Faludi, Andre Arpad; Silbiger, Vivian Nogueira; Luchessi, André Ducati; Hirata, Rosario Dominguez Crespo; Hirata, Mario Hiroyuki

doi:10.1007/s11033-023-08784-9

Cited by 1 publication

(3 citation statements)

References 47 publications

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“…This indicates that such polymorphisms, especially when inherited as a haplotype, could impact LDL-C metabolism. A recent study [ 40 ] showed that rs5742911 enhances or creates a binding site for three miRNAs (miR-3190-5p, miR-4435, and miR-4717-5p) and disrupts a binding site for miR-1587-5p, influencing gene expression and potentially contributing to FH, underscoring the significance of the findings in this study. Polymorphism rs1433099 was strongly associated with baseline TC and LDL-C levels ( P < 0.05).…”

Section: Resultssupporting

confidence: 80%

“…Furthermore, according to a Mexican study, the rs14158 A allele and the rs2738466 G allele were associated with an increased risk of acute coronary syndrome and concomitantly lower HDL-C levels [ 48 ]. Additionally, rs5742911 was potentially associated with FH by disrupting interactions with miRNAs and altering gene expression in a recent Dutch study [ 40 ]. Collectively, these findings underscore the potential for the rs14158, rs2738466, rs5742911, and rs17249057 polymorphisms to influence cholesterol metabolism in various ways between distinct populations.…”

Section: Discussionmentioning

confidence: 99%

“…However, polymorphisms in the LDLR 3’ UTR have seldom been reported in the context of patients with dyslipidemia. A recent study revealed that variations in the LDLR 3’ UTR interfere with miRNA: mRNA interactions, which may impact gene expression and could be linked to FH [ 40 ].…”

Section: Introductionmentioning

confidence: 99%

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Impact of LDLR polymorphisms on lipid levels and atorvastatin’s efficacy in a northern Chinese adult Han cohort with dyslipidemia

Zhao,

You,

Tian

et al. 2024

Lipids Health Dis

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Background Dyslipidemia, a significant risk factor for atherosclerotic cardiovascular disease (ASCVD), is influenced by genetic variations, particularly those in the low-density lipoprotein receptor (LDLR) gene. This study aimed to elucidate the effects of LDLR polymorphisms on baseline serum lipid levels and the therapeutic efficacy of atorvastatin in an adult Han population in northern China with dyslipidemia. Methods In this study, 255 Han Chinese adults receiving atorvastatin therapy were examined and followed up. The 3’ untranslated region (UTR) of the LDLR gene was sequenced to identify polymorphisms. The associations between gene polymorphisms and serum lipid levels, as well as changes in lipid levels after intervention, were evaluated using the Wilcoxon rank sum test, with a P < 0.05 indicating statistical significance. Assessment of linkage disequilibrium patterns and haplotype structures was conducted utilizing Haploview. Results Eleven distinct polymorphisms at LDLR 3’ UTR were identified. Seven polymorphisms (rs1433099, rs14158, rs2738466, rs5742911, rs17249057, rs55971831, and rs568219285) were correlated with the baseline serum lipid levels (P < 0.05). In particular, four polymorphisms (rs14158, rs2738466, rs5742911, and rs17249057) were in strong linkage disequilibrium (r2 = 1), and patients with the AGGC haplotype had higher TC and LDL-C levels at baseline. Three polymorphisms (rs1433099, rs2738467, and rs7254521) were correlated with the therapeutic efficacy of atorvastatin (P < 0.05). Furthermore, carriers of the rs2738467 T allele demonstrated a significantly greater reduction in low-density lipoprotein cholesterol (LDL-C) levels post-atorvastatin treatment (P = 0.03), indicating a potentially crucial genetic influence on therapeutic outcomes. Two polymorphisms (rs751672818 and rs566918949) were neither correlated with the baseline serum lipid levels nor atorvastatin’s efficacy. Conclusions This research outlined the complex genetic architecture surrounding LDLR 3’ UTR polymorphisms and their role in lipid metabolism and the response to atorvastatin treatment in adult Han Chinese patients with dyslipidemia, highlighting the importance of genetic profiling in enhancing tailored therapeutic strategies. Furthermore, this investigation advocates for the integration of genetic testing into the management of dyslipidemia, paving the way for customized therapeutic approaches that could significantly improve patient care. Trial registration This multicenter study was approved by the Ethics Committee of Xiangya Hospital Central South University (ethics number K22144). It was a general ethic. In addition, this study was approved by The First Hospital of Hebei Medical University (ethics number 20220418).

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Section: Resultssupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%