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The brave new world of genetic testing in the management of the dyslipidaemias

Nawawi HM, Chua YA, Watts GF

Curr Opin Cardiol, 2020 05;35(3):226-233.
PMID: 32097179 DOI: 10.1097/HCO.0000000000000721

PURPOSE OF REVIEW: With the exception of familial hypercholesterolaemia, the value of genetic testing for managing dyslipidaemias is not established. We review the genetics of major dyslipidaemias in context of clinical practice.
RECENT FINDINGS: Genetic testing for familial hypercholesterolaemia is valuable to enhance diagnostic precision, cascade testing, risk prediction and the use of new medications. Hypertriglyceridaemia may be caused by rare recessive monogenic, or by polygenic, gene variants; genetic testing may be useful in the former, for which antisense therapy targeting apoC-III has been approved. Familial high-density lipoprotein deficiency is caused by specific genetic mutations, but there is no effective therapy. Familial combined hyperlipidaemia (FCHL) is caused by polygenic variants for which there is no specific gene testing panel. Familial dysbetalipoproteinaemia is less frequent and commonly caused by APOE ε2ε2 homozygosity; as with FCHL, it is responsive to lifestyle modifications and statins or/and fibrates. Elevated lipoprotein(a) is a quantitative genetic trait whose value in risk prediction over-rides genetic testing; treatment relies on RNA therapeutics.
SUMMARY: Genetic testing is not at present commonly available for managing dyslipidaemias. Rapidly advancing technology may presage wider use, but its worth will require demonstration of cost-effectiveness and a healthcare workforce trained in genomic medicine.

Matched MeSH terms: Dyslipidemias/genetics*
Fulltext Investigating the association of CD36 gene polymorphisms (rs1761667 and rs1527483) with T2DM and dyslipidemia: Statistical analysis, machine learning based prediction, and meta-analysis

Hatmal MM, Alshaer W, Mahmoud IS, Al-Hatamleh MAI, Al-Ameer HJ, Abuyaman O, et al.

PLoS One, 2021;16(10):e0257857.
PMID: 34648514 DOI: 10.1371/journal.pone.0257857

CD36 (cluster of differentiation 36) is a membrane protein involved in lipid metabolism and has been linked to pathological conditions associated with metabolic disorders, such as diabetes and dyslipidemia. A case-control study was conducted and included 177 patients with type-2 diabetes mellitus (T2DM) and 173 control subjects to study the involvement of CD36 gene rs1761667 (G>A) and rs1527483 (C>T) polymorphisms in the pathogenesis of T2DM and dyslipidemia among Jordanian population. Lipid profile, blood sugar, gender and age were measured and recorded. Also, genotyping analysis for both polymorphisms was performed. Following statistical analysis, 10 different neural networks and machine learning (ML) tools were used to predict subjects with diabetes or dyslipidemia. Towards further understanding of the role of CD36 protein and gene in T2DM and dyslipidemia, a protein-protein interaction network and meta-analysis were carried out. For both polymorphisms, the genotypic frequencies were not significantly different between the two groups (p > 0.05). On the other hand, some ML tools like multilayer perceptron gave high prediction accuracy (≥ 0.75) and Cohen's kappa (κ) (≥ 0.5). Interestingly, in K-star tool, the accuracy and Cohen's κ values were enhanced by including the genotyping results as inputs (0.73 and 0.46, respectively, compared to 0.67 and 0.34 without including them). This study confirmed, for the first time, that there is no association between CD36 polymorphisms and T2DM or dyslipidemia among Jordanian population. Prediction of T2DM and dyslipidemia, using these extensive ML tools and based on such input data, is a promising approach for developing diagnostic and prognostic prediction models for a wide spectrum of diseases, especially based on large medical databases.

Matched MeSH terms: Dyslipidemias/genetics*
Prevalence of lipid abnormalities and attainment of normal lipid levels among patients with dyslipidaemia: a pooled analysis of observational studies from five Asian countries

Unniachan S, Bash LD, Khovidhunkit W, Sri RZ, Vicaldo E, Recto C, et al.

Int J Clin Pract, 2014 Aug;68(8):1010-9.
PMID: 24666791 DOI: 10.1111/ijcp.12407

Guidelines emphasise the importance of low-density lipoprotein cholesterol (LDL-C) goals for cardiovascular risk reduction. Given the importance of association between high-density lipoprotein (HDL-C) and triglycerides (TG) normal levels and cardiovascular risk, there is an additional need to further evaluate diverse dyslipidaemic populations.

Matched MeSH terms: Dyslipidemias/genetics
The prevention and treatment of hypoadiponectinemia-associated human diseases by up-regulation of plasma adiponectin

Hossain MM, Mukheem A, Kamarul T

Life Sci, 2015 Aug 15;135:55-67.
PMID: 25818192 DOI: 10.1016/j.lfs.2015.03.010

Hypoadiponectinemia is characterized by low plasma adiponectin levels that can be caused by genetic factors, such as single nucleotide polymorphisms (SNPs) and mutations in the adiponectin gene or by visceral fat deposition/obesity. Reports have suggested that hypoadiponectinemia is associated with dyslipidemia, hypertension, hyperuricemia, metabolic syndrome, atherosclerosis, type 2 diabetes mellitus and various cardiovascular diseases. Previous studies have highlighted several potential strategies to up-regulate adiponectin secretion and function, including visceral fat reduction through diet therapy and exercise, administration of exogenous adiponectin, treatment with peroxisome proliferator-activating receptor gamma (PPARγ) agonists (e.g., thiazolidinediones (TZDs)) and ligands (e.g., bezafibrate and fenofibrate) or the blocking of the renin-angiotensin system. Likewise, the up-regulation of the expression and stimulation of adiponectin receptors by using adiponectin receptor agonists would be an effective method to treat obesity-related conditions. Notably, adiponectin is an abundantly expressed bioactive protein that also exhibits a wide spectrum of biological properties, such as insulin-sensitizing, anti-diabetic, anti-inflammatory and anti-atherosclerotic activities. Although targeting adiponectin and its receptors has been useful for treating diabetes and other metabolic-related diseases in experimental studies, current drug development based on adiponectin/adiponectin receptors for clinical applications is scarce, and there is a lack of available clinical trial data. This comprehensive review discusses the strategies that are presently being pursued to harness the potential of adiponectin up-regulation. In addition, we examined the current status of drug development and its potential for clinical applications.

Matched MeSH terms: Dyslipidemias/genetics