The A640G CYBA polymorphism associates with subclinical atherosclerosis in diabetes

Moreno, Maria de Ujue

doi:10.2741/347

Cited by 1 publication

(1 citation statement)

References 24 publications

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“…PBMC have been reported to contain a multitude of distinct multi-potent progenitor cell populations and possess the potential to differentiate into various kinds of cells under appropriate conditions [ 30 ]. Increased ROS levels from NADPH oxidases in PBMC has been associated with several pathogeneses, including chronic obstructive pulmonary disease [ 31 ], type 2 diabetes [ 32 ], coagulation activation [ 33 ], endothelial dysfunction [ 34 ] and hypertension [ 35 ]. Therefore, the formation of ROS and oxidative stress in PBMC may be one of mechanisms linking caloric restriction and its possible effects on human health.…”

Section: Introductionmentioning

confidence: 99%

Polymorphism of rs1836882 in NOX4 Gene Modifies Associations between Dietary Caloric Intake and ROS Levels in Peripheral Blood Mononuclear Cells

Liu

Wang

et al. 2013

PLoS ONE

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Excessive caloric intake is a contributing risk factor for human metabolic disorders. Caloric restriction may prolong a person’s life by lowering the incidence of deadly diseases. Reactive oxygen species (ROS) in peripheral blood mononuclear cells (PBMC) have been associated with the biochemical basis of the relationship between caloric intake and pathophysiologic processes. Polymorphisms associated with ROS generation genes are being increasingly implicated in inter-individual responses to daily caloric intake alterations. In the current study, a single nucleotide polymorphism, rs1836882, in the nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) gene’s promoter region was found to modulate associations between dietary caloric intake and ROS levels in PBMC. Based on rs1836882, 656 Chinese Han participants were classified into CC, CT and TT genotypes. ROS levels in PBMC were significantly higher in the CC or CT genotypes compared with the TT genotype with the same increases in daily caloric intake. Using an electrophoretic mobility shift assay, NOX4 promoter region with rs1836882 (T) was observed to have a higher affinity for hepatocyte nuclear factor gamma (HNF3γ) protein than rs1836882 (C). HNF3γ protein over-expression decreased NOX4 gene transcriptional activity in the TT genotype more than in the CC genotype (5.68% vs. 2.12%, P<0.05) in a dual luciferase reporter assay. By silencing the NOX4 gene using small interfering RNA or over-expressing HNF3γ using an expression plasmid, serum from high dietary caloric intake participants decreased ROS levels in PBMC of the TT genotype more than in the CC or CT genotype via HNF3γ down-regulating the NOX4 gene expression signaling pathway. This is the first study to report on the functions of phenotypes of rs1836882 in the NOX4 gene, and it suggests rs1836882 as a candidate gene for interpreting inter-individual ROS levels differences in PBMC induced by alterations in daily caloric intake.

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