High Frequency of a Retinoid X Receptor γ Gene Variant in Familial Combined Hyperlipidemia That Associates With Atherogenic Dyslipidemia

Nohara, Atsushi; Kawashiri, Masa‐aki; Claudel, Thierry; Mizuno, Mihoko; Tsuchida, Masayuki; Takata, Munehisa; Katsuda, Shoji; Miwa, Kenji; Inazu, Akihiro; Kuipers, Folkert; Kobayashi, Junji; Koizumi, Junji; Yamagishi, Masakazu; Mabuchi, Hiroshi

doi:10.1161/01.atv.0000258945.76141.8a

Cited by 20 publications

(14 citation statements)

References 52 publications

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“…CD163 antigen, a member of the scavenger receptor cysteine-rich (SRCR) super family class B [32], distal-less homeobox 5 (DLX5) responsible for proliferation of tumor cells [33] and insulin-like growth factor binding protein 5 (IGFBP5) isoform 2 found in breast cancer [34] were also identified in ALC formation. Thyroid hormone-responsive protein (THRSP) previously reported in adipogenesis [35,36] and retinoic acid receptor RXR-gamma associated with familial combined hyperlipidemia [37] were identified during adipogenesis. FABP4 and CD36 which encode lipid transporters [38,39] were up-regulated in all tissues.…”

Section: Discussionmentioning

confidence: 99%

Depot-specific gene expression profiles during differentiation and transdifferentiation of bovine muscle satellite cells, and differentiation of preadipocytes

Lee

Lee²,

Kamli

et al. 2012

Genomics

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We report a systematic study of gene expression during myogenesis and transdifferentiation in four bovine muscle tissues and of adipogenesis in three bovine fat tissues using DNA microarray analysis. One hundred hybridizations were performed and 7245 genes of known and unknown function were identified as being differentially expressed. Supervised hierarchical cluster analysis of gene expression patterns revealed the tissue specificity of genes. A close relationship in global gene expression observed for adipocyte-like cells derived from muscle and adipocytes derived from intramuscular fat suggests a common origin for these cells. The role of transthyretin in myogenesis is a novel finding. Different genes were highly induced during the transdifferentiation of myogenic satellite cells and in the adipogenesis of preadipocytes, indicating the involvement of different molecular mechanisms in these processes. Induction of CD36 and FABP4 expression in adipocyte-like cells and adipocytes may share a common pathway.

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Section: Discussionmentioning

confidence: 99%

Depot-specific gene expression profiles during differentiation and transdifferentiation of bovine muscle satellite cells, and differentiation of preadipocytes

Lee

Lee²,

Kamli

et al. 2012

Genomics

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“…Pparg has been implicated in atherosclerosis (36), coronary heart disease (37) and hypertension (38). RXRs are members of the NR2B family of nuclear receptors and are major heterodimerization partners of PPARs (39). RXRs are involved in mediating the anti-proliferative effects of retinoic acid, which can comprise a collection of molecules with retinoids to maintain homeostasis in adults (40).…”

Section: Discussionmentioning

confidence: 99%

“…A growing number of studies have reported the role of RXRs and PPARs in controlling cellular metabolism in tissues, including the myocardium (40,41). Nohara et al (39) suggested that a variant of Rxrg contributes to human genetic dyslipidemia. Taken together, the TFs, Pparg and Rxrg, may have utility in the diagnose and treatment of hypertension.…”

Section: Discussionmentioning

confidence: 99%

Prediction of marker genes associated with hypertension by bioinformatics analyses

Gao

Jia

et al. 2017

International Journal of Molecular Medicine

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This study aimed to explore the underlying marker genes associated with hypertension by bioinformatics analyses. A gene expression profile (GSE54015) was downloaded. The differentially expressed genes (DEGs) between the normotensive female (NF) and hypertensive female (HF), and between the normotensive male (NM) and hypertensive male (HM) groups were analyzed. Gene Ontology (GO) and pathway enrichment analyses were performed, followed by protein-protein interaction (PPI) network construction. The transcription factors (TFs), and the common DEGs between the HF and HM groups were then analyzed. In total, 411 DEGs were identified between the HF and NF groups, and 418 DEGs were identified between the HM and NM groups. The upregulated DEGs in the HF and HM groups were enriched in 9 GO terms, including oxidation reduction, such as cytochrome P450, family 4, subfamily b, polypeptide 1 (Cyp4b1) and cytochrome P450, family 4, subfamily a, polypeptide 31 Cyp4a31). The downregulated DEGs were mainly enriched in GO terms related to hormone metabolic processes. In the PPI network, cytochrome P450, family 2, subfamily e, polypeptide 1 (Cyp2e1) had the highest degree in all 3 analysis methods in the HF group. Additionally, 4 TFs were indentified from the 2 groups of data, including sterol regulatory element binding transcription factor 1 (Srebf1), estrogen receptor 1 (Esr1), retinoid X receptor gamma (Rxrg) and peroxisome proliferator-activated receptor gamma (Pparg). The intersection genes were mainly enriched in GO terms related to the extracellular region. On the whole, our data indicate that the DEGs, Cyp4b1, Cyp4a31 and Loxl2, and the TFs, Esr1, Pparg and Rxrg, are associated with the progression of hypertension, and may thus serve as potential therapeutic targets in this disease.

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“…FCHL family members exhibit varying degrees of dyslipidemia with either isolated high triglycerides, LDL cholesterol, or both, which is another feature of FCHL. Several candidate genes have been reported, such as upstream stimulatory factor 1 (USF1) 21) , apoA5 22) , Retinoid X receptor- 23) , hepatic lipase 24) , and so forth. The diagnostic criteria for FCHL in Japan are as follows:…”

Section: Familial Combined Hyperlipidemia (Fchl)mentioning

confidence: 99%

Management of Type IIb Dyslipidemia

Arai

Ishibashi

Bujo

et al. 2012

JAT

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Although the Japan Atherosclerosis Society guideline for the diagnosis and prevention of atherosclerosis cardiovascular diseases for the Japanese population provides targets for low-density lipoprotein (LDL) cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol to prevent cardiovascular disease in patients with dyslipidemia, there is no guideline specifically targeting the treatment of type b dyslipidemia, which is one of the most common types of dyslipidemia, along with type a and type dyslipidemia. Type b dyslipidemia is important because it sometimes accompanies atherogenic lipid profiles, such as small, dense LDL, remnants, low HDL cholesterolemia. It is also associated with type 2 diabetes mellitus, metabolic syndrome, and chronic kidney disease (CKD), and most patients with familial combined hyperlipidemia (FCHL) show this phenotype; therefore, it is assumed that patients with type b dyslipidemia have a high risk for cardiovascular disease. Thus, the management of type b dyslipidemia is very important for the prevention of cardiovascular disease, so we have attempted to provide a guideline for the management of type b dyslipidemia.

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High Frequency of a Retinoid X Receptor γ Gene Variant in Familial Combined Hyperlipidemia That Associates With Atherogenic Dyslipidemia

Abstract: Objective-The genetic background of familial combined hyperlipidemia (FCHL) has not been fully clarified. Because several nuclear receptors play pivotal roles in lipid metabolism, we tested the hypothesis that genetic variants of nuclear receptors contribute to FCHL.

Cited by 20 publications

References 52 publications

Depot-specific gene expression profiles during differentiation and transdifferentiation of bovine muscle satellite cells, and differentiation of preadipocytes

Depot-specific gene expression profiles during differentiation and transdifferentiation of bovine muscle satellite cells, and differentiation of preadipocytes

Prediction of marker genes associated with hypertension by bioinformatics analyses

Management of Type IIb Dyslipidemia

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