PPARα gene polymorphisms modulate the association between physical activity and cardiometabolic risk

Halder, Indrani; Champlin, John; Sheu, Lei K.; Goodpaster, Bret H.; Manuck, Stephen B.; Ferrell, Robert E.; Muldoon, Matthew F.

doi:10.1016/j.numecd.2014.02.007

Cited by 5 publications

(5 citation statements)

References 29 publications

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“…In these studies, C allele homozygotes had a significantly greater left ventricular mass index compared with G allele homozygotes and C allele heterozygotes, which was greater in hypertensive subjects [133]. Moreover, Halder et al found that the presence of the G allele of rs135542 was associated with higher cardiometabolic risk [134]. Another report found a significant association between rs135551 and myocardial infarction and an association trend between rs135543 and myocardial infarction [135].…”

Section: Association Of Pparα Polymorphisms With Cardiovascular Diseasesmentioning

confidence: 95%

Targeting PPARα for the Treatment and Understanding of Cardiovascular Diseases

Yang

et al. 2018

Cell Physiol Biochem

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Three members of the peroxisome proliferator-activated receptor (PPAR) family, PPARα, PPARγ, and PPARβ/δ, have been investigated widely over the past few decades. Although the roles of these PPARs and their agonists/antagonists were defined in clinical and basic studies, the conflicting results from these studies indicate that more analysis is needed to understand the roles of PPARs. PPARα is a ligand-activated transcription factor that contributes to the regulation of a variety of processes, ranging from inflammation and immunity to nutrient metabolism and energy homeostasis. In this review, we focus on the function and mechanisms of PPARα in the cardiovascular system under various pathological conditions, including vascular and heart injury, blood pressure regulation, and lipid disorder-related cardiovascular injury, as well as its polymorphisms and pharmacogenetic associations with cardiovascular diseases. The anti-inflammatory effect of PPARα in cardiovascular injury is mainly through inhibition of pro-inflammatory signaling pathways and improvement of the lipid profile. Moreover, PPARα also modulates the activity of endothelial nitric oxide synthase and resets the renin-angiotensin system to regulate vascular tone. PPARα gene variants appear to be associated with some cardiovascular risk factors, such as higher plasma lipid levels, cardiac growth, and increased risk of coronary artery disease. Nowadays, novel PPARα drugs with broad safety margins and therapeutic potential for metabolic syndrome and cardiovascular diseases are being developed and applied in the clinical setting. The insights from the current review shed new light on areas of further study and provide a better understanding of the role of PPARα in cardiovascular diseases.

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Section: Association Of Pparα Polymorphisms With Cardiovascular Diseasesmentioning

confidence: 95%

Targeting PPARα for the Treatment and Understanding of Cardiovascular Diseases

Yang

et al. 2018

Cell Physiol Biochem

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“…Halder et al . [ 23 ] showed rs135542 to influence habitual physical activity and cardiometabolic risk.…”

Section: Discussionmentioning

confidence: 99%

Peroxisome Proliferator-Activated Receptor α and γ Gene Polymorphisms among South Indian Patients with Diabetic Dyslipidaemia

Kamalanathan¹,

Bage²,

Selvarajan³

et al. 2023

Indian Journal of Endocrinology and Metabolism

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Background: Peroxisome proliferator-activated receptors (PPAR) α and γ genes play an important role in dyslipidaemia of T2DM. Aims: To estimate the frequency distribution of PPAR α and γ gene polymorphisms in South Indian T2DM patients with dyslipidaemia compared to healthy controls. Normative frequencies of SNPs were established and compared with data for 1000 genome populations. Methods: Eligible 382 cases and 336 age and sex-matched controls were enrolled. Six SNPs in PPARα [rs1800206 C>G (Leu162Val), rs4253778 G>C, rs135542 T>C] and PPARγ [rs3856806 (C>T), rs10865710 (C>G), rs1805192 C>G (Pro12Ala)] genes were selected for genotyping. Results: The allele and gene frequencies did not significantly differ between the diabetic dyslipidaemia cases and healthy controls. However, they were significantly different from that of 1000 genome populations except for rs1800206 C>G (Leu162Val) and rs1805192 C>G (Pro12Ala). Conclusion: The studied polymorphisms in PPARα and PPARγ genes are not associated with diabetic dyslipidaemia among South Indian patients.

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“…In addition, PPARα participates in mitochondrial-mediated energy metabolism [ 51 ] and can also regulate the synthesis of very low-density lipoproteins to improve blood lipids [ 52 ]. In many clinical studies, PPARα has also been linked to the start of cardiovascular disease, atherosclerotic alterations, and hypertension in numerous clinical trials [ 53 , 54 , 55 , 56 ]. In the current research, the exploration and clinical intervention of PPAR α also focuses on PO.…”

Section: Discussionmentioning

confidence: 99%

Identification of Differential Expression Genes between Volume and Pressure Overloaded Hearts Based on Bioinformatics Analysis

Zhao

Zhou

et al. 2022

Genes

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Volume overload (VO) and pressure overload (PO) are two common pathophysiological conditions associated with cardiac disease. VO, in particular, often occurs in a number of diseases, and no clinically meaningful molecular marker has yet been established. We intend to find the main differential gene expression using bioinformatics analysis. GSE97363 and GSE52796 are the two gene expression array datasets related with VO and PO, respectively. The LIMMA algorithm was used to identify differentially expressed genes (DEGs) of VO and PO. The DEGs were divided into three groups and subjected to functional enrichment analysis, which comprised GO analysis, KEGG analysis, and the protein–protein interaction (PPI) network. To validate the sequencing data, cardiomyocytes from AR and TAC mouse models were used to extract RNA for qRT-PCR. The three genes with random absolute values of LogFC and indicators of heart failure (natriuretic peptide B, NPPB) were detected: carboxylesterase 1D (CES1D), whirlin (WHRN), and WNK lysine deficient protein kinase 2 (WNK2). The DEGs in VO and PO were determined to be 2761 and 1093, respectively, in this study. Following the intersection, 305 genes were obtained, 255 of which expressed the opposing regulation and 50 of which expressed the same regulation. According to the GO and pathway enrichment studies, DEGs with opposing regulation are mostly common in fatty acid degradation, propanoate metabolism, and other signaling pathways. Finally, we used Cytoscape’s three techniques to identify six hub genes by intersecting 255 with the opposite expression and constructing a PPI network. Peroxisome proliferator-activated receptor (PPARα), acyl-CoA dehydrogenase medium chain (ACADM), patatin-like phospholipase domain containing 2 (PNPLA2), isocitrate dehydrogenase 3 (IDH3), heat shock protein family D member 1 (HSPD1), and dihydrolipoamide S-acetyltransferase (DLAT) were identified as six potential genes. Furthermore, we predict that the hub genes PPARα, ACADM, and PNPLA2 regulate VO myocardial changes via fatty acid metabolism and acyl-Coa dehydrogenase activity, and that these genes could be employed as basic biomarkers for VO diagnosis and treatment.

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PPARα gene polymorphisms modulate the association between physical activity and cardiometabolic risk

Cited by 5 publications

References 29 publications

Targeting PPARα for the Treatment and Understanding of Cardiovascular Diseases

Targeting PPARα for the Treatment and Understanding of Cardiovascular Diseases

Peroxisome Proliferator-Activated Receptor α and γ Gene Polymorphisms among South Indian Patients with Diabetic Dyslipidaemia

Identification of Differential Expression Genes between Volume and Pressure Overloaded Hearts Based on Bioinformatics Analysis

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