Polymorphisms in glucose homeostasis genes are associated with cardiovascular and renal parameters in patients with diabetic nephropathy

Mota-Zamorano, Sonia; González, Luz María; Robles, Nicolás Roberto; Valdivielso, José M.; Arévalo-Lorido, José Carlos; López‐Gómez, Juan M.; Gervasini, Guillermo

doi:10.1080/07853890.2022.2138531

Cited by 3 publications

(2 citation statements)

References 61 publications

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“…These overlapping peaks were most significantly enriched for the ZNF460 TF binding motif ( Fig 3C ). While little has been reported on ZNF460, either in general or specifically in adipocytes, a an intronic variant in GLUT1 (rs841848) that has been associated with diabetic complications [ 49 – 51 ] and multiple glucose-related traits [ 52 ], is predicted to destroy a binding site for ZNF460 and has been associated with reduced GLUT1 expression [ 53 ]. Other enriched motifs in PPARγ overlapping sites were ELK1, which has been linked to obesity as a target of miRNAs involved in adipogenesis, with decreased expression in obese visceral adipose tissue (VAT) [ 54 ], and TP73, which alters glycolysis within the liver via regulation of G6PD and other metabolic enzymes [ 55 ].…”

Section: Discussionmentioning

confidence: 99%

Molecular regulation of PPARγ/RXRα signaling by the novel cofactor ZFP407

Charrier,

Ockunzzi,

Main

et al. 2024

PLoS ONE

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Cofactors interacting with PPARγ can regulate adipogenesis and adipocyte metabolism by modulating the transcriptional activity and selectivity of PPARγ signaling. ZFP407 was previously demonstrated to regulate PPARγ target genes such as GLUT4, and its overexpression improved glucose homeostasis in mice. Here, using a series of molecular assays, including protein-interaction studies, mutagenesis, and ChIP-seq, ZFP407 was found to interact with the PPARγ/RXRα protein complex in the nucleus of adipocytes. Consistent with this observation, ZFP407 ChIP-seq peaks significantly overlapped with PPARγ ChIP-seq peaks, with more than half of ZFP407 peaks overlapping with PPARγ peaks. Transcription factor binding motifs enriched in these overlapping sites included CTCF, RARα/RXRγ, TP73, and ELK1, which regulate cellular development and function within adipocytes. Site-directed mutagenesis of frequent PPARγ phosphorylation or SUMOylation sites did not prevent its regulation by ZFP407, while mutagenesis of ZFP407 domains potentially necessary for RXR and PPARγ binding abrogated any impact of ZFP407 on PPARγ activity. These data suggest that ZFP407 controls the activity of PPARγ, but does so independently of post-translational modifications, likely by direct binding, establishing ZFP407 as a newly identified PPARγ cofactor. In addition, ZFP407 ChIP-seq analyses identified regions that did not overlap with PPARγ peaks. These non-overlapping peaks were significantly enriched for the transcription factor binding motifs of TBX19, PAX8, HSF4, and ZKSCAN3, which may contribute to the PPARγ-independent functions of ZFP407 in adipocytes and other cell types.

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Section: Discussionmentioning

confidence: 99%

Molecular regulation of PPARγ/RXRα signaling by the novel cofactor ZFP407

Charrier,

Ockunzzi,

Main

et al. 2024

PLoS ONE

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“…In T2DM patients, SNP rs8192675 in the SLC2A2 gene was related with a better glucose response. The rs8192675 SNP was documented in the global studies, and both positive and negative associations were documented within different ethnicities [13,15,16,[28][29][30][31][32]. None of the meta-analysis studies have been focused towards rs8192675 and T2DM.…”

Section: Discussionmentioning

confidence: 99%

Examining the Genetic Role of rs8192675 Variant in Saudi Women Diagnosed with Polycystic Ovary Syndrome

Alsobaie,

Alageel,

Ishfaq

et al. 2023

Diagnostics

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Polycystic ovary syndrome is a complex disorder defined by the Rotterdam criteria. Insulin resistance is a common factor for the development of type 2 diabetes mellitus among women with PCOS. The SLC2A2 gene has been identified as a T2DM gene by genome-wide association studies in the rs8192675 SNP. This study aimed to investigate the rs8192675 SNP in women diagnosed with PCOS on a molecular level and further for T2DM development in the Saudi women. In this case-control study, 100 PCOS women and 100 healthy controls were selected. Among 100 PCOS women, 28 women showed T2DM development. Genotyping for rs8192675 SNP was performed by PCR-RFLP analysis. Additionally, Sanger sequencing was performed to validate the RFLP analysis. The obtained data were used for a statistical analysis for the genotype and allele frequencies, logistic regression, and ANOVA analysis. The clinical data confirmed the positive association between FBG, FI, FSH, TT, TC, HDLc, LDLc, and family histories (p < 0.05). HWE analysis was associated in both the PCOS cases and the control individuals. Genotype and allele frequencies were associated in PCOS women and strongly associated with women with PCOS who developed T2DM (p < 0.05). No association was found in the logistic regression model or ANOVA analysis studied in women with PCOS (p > 0.05). A strong association was observed between the rs8192675 SNP and women with PCOS who developed T2DM using ANOVA analysis (p < 0.05). This study confirms that the rs8192675 SNP is associated with women with PCOS and strongly associated with women with PCOS with developed T2DM in Saudi Arabia.

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