A prevalent caveolin-1 gene variant is associated with the metabolic syndrome in Caucasians and Hispanics

Baudrand, René; Goodarzi, Mark O.; Vaidya, Anand; Underwood, Patricia; Williams, Jonathan S.; Jeunemaı̂tre, Xavier; Hopkins, Paul N.; Brown, Nancy J.; Raby, Benjamin A.; Lasky‐Su, Jessica; Adler, Gail K.; Cui, Jinrui; Guo, Xiuqing; Taylor, Kent D.; Chen, Yii Der I.; Xiang, Anny H.; Raffel, Leslie J.; Buchanan, Thomas A.; Rotter, Jerome I.; Williams, Gordon H.; Pojoga, Luminita H.

doi:10.1016/j.metabol.2015.09.005

Cited by 39 publications

(62 citation statements)

References 42 publications

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“…In a multiple regression model, sodium‐modulated aldosterone suppression‐to‐stimulation index levels were significantly higher in CAV1 minor allele carriers compared with noncarriers, even when adjusted by age, sex, body mass index, and site of study (β=0.06, P =0.04). Moreover, in adjusted logistic regression, minor allele carriers had higher odds of having IR (odds ratio 2.36 [95% CI 1.50–3.69]) and low HDL (odds ratio 1.54 [95% CI 1.01–3.37]), consistent with our previous reports on normal sodium diet . There were no differences by genotype in aldosterone or cortisol (Table ) or in resistin, adiponectin, or 24‐hour urinary sodium (data not shown).…”

Section: Resultssupporting

confidence: 90%

“…Moreover, in adjusted logistic regression, minor allele carriers had higher odds of having IR (odds ratio 2.36 [95% CI 1.50-3.69]) and low HDL (odds ratio 1.54 [95% CI 1.01-3.37]), consistent with our previous reports on normal sodium diet. 11,12 There were no differences by genotype in aldosterone or cortisol ( Table 2) or in resistin, adiponectin, or 24-hour urinary sodium (data not shown).…”

Section: Clinical and Biochemical Characteristics Categorized By Cav1mentioning

confidence: 89%

“…We previously published findings that caveolin 1 (cav-1) gene variants were associated with IR, dyslipidemia, diabetes mellitus, and metabolic syndrome in two human hypertensive cohorts. 11,12 In addition, we and others have shown that cav-1 knockout (KO) mice display several metabolic abnormalities, including hyperglycemia, IR, and dyslipidemia, although they are not obese. [13][14][15] Cav-1 is an important component of the plasma membrane and interacts with multiple signaling pathways, including steroid receptors.…”

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confidence: 99%

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Caveolin 1 Modulates Aldosterone‐Mediated Pathways of Glucose and Lipid Homeostasis

Baudrand

Gupta

Garza

et al. 2016

JAHA

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BackgroundOveractivation of the aldosterone and mineralocorticoid receptor (MR) pathway is associated with hyperglycemia and dyslipidemia. Caveolin 1 (cav‐1) is involved in glucose/lipid homeostasis and may modulate MR signaling. We investigated the interplay between cav‐1 and aldosterone signaling in modulating insulin resistance and dyslipidemia in cav‐1–null mice and humans with a prevalent variant in the CAV1 gene.Methods and ResultsIn mouse studies, cav‐1 knockout mice exhibited higher levels of homeostatic model assessment of insulin resistance, cholesterol, and resistin and lower ratios of high‐ to low‐density lipoprotein (all P<0.001 versus wild type). Moreover, cav‐1 knockout mice displayed hypertriglyceridemia and higher mRNA levels for resistin, retinol binding protein 4, NADPH oxidase 4, and aldose reductase in liver and/or fat tissues. MR blockade with eplerenone significantly decreased glycemia (P<0.01), total cholesterol (P<0.05), resistin (P<0.05), and described enzymes, with no effect on insulin or triglycerides. In the human study, we analyzed the CAV1 gene polymorphism rs926198 in 556 white participants; 58% were minor allele carriers and displayed higher odds of insulin resistance (odds ratio 2.26 [95% CI 1.40–3.64]) and low high‐density lipoprotein (odds ratio 1.54 [95% CI 1.01–3.37]). Aldosterone levels correlated with higher homeostatic model assessment of insulin resistance and resistin and lower high‐density lipoprotein only in minor allele carriers. CAV1 gene expression quantitative trait loci data revealed lower cav‐1 expression in adipose tissues by the rs926198 minor allele.ConclusionsOur findings in mice and humans suggested that decreased cav‐1 expression may activate the effect of aldosterone/MR signaling on several pathways of glycemia, dyslipidemia, and resistin. In contrast, hyperinsulinemia and hypertriglyceridemia are likely mediated by MR‐independent mechanisms. Future human studies will elucidate the clinical relevance of MR blockade in patients with genotype‐mediated cav‐1 deficiency.

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Section: Resultssupporting

confidence: 90%

Section: Clinical and Biochemical Characteristics Categorized By Cav1mentioning

confidence: 89%

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confidence: 99%

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Caveolin 1 Modulates Aldosterone‐Mediated Pathways of Glucose and Lipid Homeostasis

Baudrand

Gupta

Garza

et al. 2016

JAHA

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“…Unlike the other SNP hits in this study, TBX15 did not differ by gender[139]. Candidate gene studies have shown that CAV1 polymorphisms resulting in decreased expression of the gene are associated with insulin resistance and the metabolic syndrome in Hispanic and Caucasian cohorts[140, 141]. …”

Section: Risk Factors For Af: Hypertension Obesity and Common Genetimentioning

confidence: 76%

Genomics of Atrial Fibrillation

Gutiérrez

Chung

2016

Curr Cardiol Rep

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Atrial fibrillation (AF) is a common clinical arrhythmia that appears to be highly heritable, despite representing a complex interplay of several disease processes that generally do not manifest until later in life. In this manuscript we will review the genetic basis of this complex trait established through studies of familial AF, linkage and candidate gene studies of common AF, genome wide association studies (GWAS) of common AF, and transcriptomic studies of AF. Since AF is associated with a five-fold increase in the risk of stroke, we also review the intersection of common genetic factors associated with both of these conditions. Similarly, we highlight the intersection of common genetic markers associated with some risk factors for AF, such as hypertension and obesity, and AF. Lastly, we describe a paradigm where genetic factors predispose to the risk of AF, but which may require additional stress and trigger factors in older age to allow for the clinical manifestation of AF.

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“…While the MC2R gene acts on adrenal steroidogenesis and regulation of the glucocorticoid axis, the MC5R gene regulates the function of sebaceous glands with effect on water repulsion and thermoregulation 56 . In turn, the CIB1 gene encodes a protein involved in cell proliferation, particularly proplatelets, therefore acting on thrombopoiesis 57 , while the CAV1 gene has a critical role in signal transduction and trafficking for its interplay with steroid receptors and is associated with the metabolic syndrome in humans 58 .…”

Section: Discussionmentioning

confidence: 99%

Genomic scan of selective sweeps in Djallonké (West African Dwarf) sheep shed light on adaptation to harsh environments

Álvarez

Traoré

Pérez‐Pardal

et al. 2020

Sci Rep

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the Djallonké (West African Dwarf) sheep is a small-sized haired sheep resulting from a costly evolutionary process of natural adaptation to the harsh environment of West Africa including trypanosome challenge. However, genomic studies carried out in this sheep are scant. in this research, genomic data of 184 Djallonké sheep (and 12 Burkina-Sahel sheep as an outgroup) generated using medium-density SNP Chips were analyzed. Three different statistics (iHS, XP-EHH and nSL) were applied to identify candidate selection sweep regions spanning genes putatively associated with adaptation of sheep to the West African environment. A total of 207 candidate selection sweep regions were defined. Gene-annotation enrichment and functional annotation analyses allowed to identify three statistically significant functional clusters involving 12 candidate genes. Genes included in functional clusters associated to selection signatures were mainly related to metabolic response to stress, including regulation of oxidative and metabolic stress and thermotolerance. the bovine chromosomal areas carrying QtLs for cattle trypanotolerance were compared with the regions on which the orthologous functional candidate cattle genes were located. The importance of cattle BTA4 for trypanotolerant response might have been conserved between species. the current research provides new insights on the genomic basis for adaptation and highlights the importance of obtaining information from non-cosmopolite livestock populations managed in harsh environments.Drift and selection may cause selective sweep signatures on the genome, characterized by reduced diversity and extensive linkage disequilibrium. Favorable alleles increase in frequency more rapidly than expected for a neutral genetic scenario and further alter the allele frequencies of genomic variants near the beneficial mutation.

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A prevalent caveolin-1 gene variant is associated with the metabolic syndrome in Caucasians and Hispanics

Cited by 39 publications

References 42 publications

Caveolin 1 Modulates Aldosterone‐Mediated Pathways of Glucose and Lipid Homeostasis

Caveolin 1 Modulates Aldosterone‐Mediated Pathways of Glucose and Lipid Homeostasis

Genomics of Atrial Fibrillation

Genomic scan of selective sweeps in Djallonké (West African Dwarf) sheep shed light on adaptation to harsh environments

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