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Here the authors defined the functional activity of common variant C+87T in the 3′-UTR of the CHGA mRNA, which has been associated with both BP elevation in the population and risk for hypertensive (nondiabetic) renal disease
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In this report, common variants and haplotypes of the CHGB promoter were functionally defined in transcriptional assays; such variants were strongly predictive of autonomic activity and BP in vivo
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This was the initial report on the effect of CHGA polymorphisms on susceptibility to hypertensive renal disease in African Americans. The functional variant was at position C+87T in the CHGA mRNA
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CHGA expression displays paradoxic relationships with BP: though human essential hypertension is associated with elevated plasma CHGA, targeted ablation of the Chga locus in the mouse also results in hypertension. In this study, the authors used gene targeting and replacement to systematically vary the copy number of CHGA from 0 to 4 copies per diploid genome, and the results established biphasic effects of CHGA copy number on catecholamine storage and release as well as on BP
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Targeted ablation of the Chga locus results in systemic hypertension in the mouse; this study defined widespread effects of such genetic deletion upon both the sympathetic and parasympathetic branches of the autonomic nervous system
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Adjustment of heart rate upwards or downwards in response to endogenous and exogenous cues (heart rate variability, HRV) reflects a healthy autonomic system. After targeted ablation of the Chga gene in the mouse, HRV declines; the trait can be "rescued" by replacement of the catestatin fragment of CHGA
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In the mouse, knockout of the Chga gene (Chga-/- genotype) results in a peculiar combination of elevated blood pressure coupled with enhanced insulin sensitivity, especially in the liver. Chga encodes a dysglycemic fragment, named "pancreastatin"; administration of this peptide to Chga-/- mice reversed the insulin sensitivity of the knockout state
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• Gayen JR, Saberi M, Schenk S, et al.: A novel pathway of insulin sensitivity in chromogranin A null mice: a crucial role for pancreastatin in glucose homeostasis. J Biol Chem 2009, 284:28498-28509. In the mouse, knockout of the Chga gene (Chga-/- genotype) results in a peculiar combination of elevated blood pressure coupled with enhanced insulin sensitivity, especially in the liver. Chga encodes a dysglycemic fragment, named "pancreastatin" ; administration of this peptide to Chga-/- mice reversed the insulin sensitivity of the knockout state.
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Here the authors profiled the transcriptome in mice after targeted ablation of the Chga locus, and thereby identified global patterns of mRNA expression subserving enhanced insulin sensitivity in this animal model
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Here the authors defined commonly occurring, natural genetic variation across the human CHGB locus, including promoter variants predicting elevated BP. In a complementary study, targeted ablation of the mouse Chgb locus resulted in systemic hypertension
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