Dataset Information

The TRIB3 R84 variant is associated with increased left ventricular mass in a sample of 2426 White individuals.

ABSTRACT:

Background

Prior studies in animal models showed that increased cardiac expression of TRIB3 has a pathogenic role in inducing left ventricular mass (LVM). Whether alterations in TRIB3 expression or function have a pathogenic role in inducing LVM increase also in humans is still unsettled. In order to address this issue, we took advantage of a nonsynonymous TRIB3 Q84R polymorphism (rs2295490), a gain-of-function amino acid substitution impairing insulin signalling, and action in primary human endothelial cells which has been associated with insulin resistance, and early vascular atherosclerosis.

Methods

SNP rs2295490 was genotyped in 2426 White adults in whom LVM index (LVMI) was assessed by validated echocardiography-derived measures.

Results

After adjusting for age and sex, LVMI progressively and significantly increased from 108 to 113, to 125 g/m² in Q84Q, Q84R, and R84R individuals, respectively (Q84R vs. Q84Q, P = 0.03; R84R vs. Q84Q, P < 0.0001). The association between LVMI and the Q84R and R84R genotype remained significant after adjusting for blood pressure, smoking habit, fasting glucose levels, glucose tolerance status, anti-hypertensive treatments, and lipid-lowering therapy (Q84R vs. Q84Q, P = 0.01; R84R vs. Q84Q, P < 0.0001).

Conclusions

We found that the gain-of-function TRIB3 Q84R variant is significantly associated with left ventricular mass in a large sample of White nondiabetic individual of European ancestry.

SUBMITTER: Mannino GC

PROVIDER: S-EPMC8164223 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Publications

The TRIB3 R84 variant is associated with increased left ventricular mass in a sample of 2426 White individuals.

Mannino Gaia Chiara GC Averta Carolina C Fiorentino Teresa Vanessa TV Succurro Elena E Spiga Rosangela R Mancuso Elettra E Miceli Sofia S Perticone Maria M Sciacqua Angela A Andreozzi Francesco F Sesti Giorgio G

Cardiovascular diabetology 20210529 1

<h4>Background</h4>Prior studies in animal models showed that increased cardiac expression of TRIB3 has a pathogenic role in inducing left ventricular mass (LVM). Whether alterations in TRIB3 expression or function have a pathogenic role in inducing LVM increase also in humans is still unsettled. In order to address this issue, we took advantage of a nonsynonymous TRIB3 Q84R polymorphism (rs2295490), a gain-of-function amino acid substitution impairing insulin signalling, and action in primary h ...[more]

PMID: 34051802

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Project description:Background and purposeLeft ventricular (LV) mass index is a marker of subclinical LV remodeling that relates to white matter damage in aging, but molecular pathways underlying this association are unknown. This study assessed if LV mass index related to cerebrospinal fluid (CSF) biomarkers of microglial activation (sTREM2 [soluble triggering receptor expressed on myeloid cells 2]), axonal injury (NFL [neurofilament light]), neurodegeneration (total-tau), and amyloid-β, and whether these biomarkers partially accounted for associations between increased LV mass index and white matter damage. We hypothesized higher LV mass index would relate to greater CSF biomarker levels, and these pathologies would partially mediate associations with cerebral white matter microstructure.MethodsVanderbilt Memory and Aging Project participants who underwent cardiac magnetic resonance, lumbar puncture, and diffusion tensor imaging (n=142, 72±6 years, 37% mild cognitive impairment [MCI], 32% APOE-ε4 positive, LV mass index 51.4±8.1 g/m2, NFL 1070±588 pg/mL) were included. Linear regressions and voxel-wise analyses related LV mass index to each biomarker and diffusion tensor imaging metrics, respectively. Follow-up models assessed interactions with MCI and APOE-ε4. In models where LV mass index significantly related to a biomarker and white matter microstructure, we assessed if the biomarker mediated white matter associations.ResultsAmong all participants, LV mass index was unrelated to CSF biomarkers (P>0.33). LV mass index interacted with MCI (P=0.01), such that higher LV mass index related to increased NFL among MCI participants. Associations were also present among APOE-ε4 carriers (P=0.02). NFL partially mediated up to 13% of the effect of increased LV mass index on white matter damage.ConclusionsSubclinical cardiovascular remodeling, measured as an increase in LV mass index, is associated with neuroaxonal degeneration among individuals with MCI and APOE-ε4. Neuroaxonal degeneration partially reflects associations between higher LV mass index and white matter damage. Findings highlight neuroaxonal degeneration, rather than amyloidosis or microglia, may be more relevant in pathways between structural cardiovascular remodeling and white matter damage.

Dataset Information

The TRIB3 R84 variant is associated with increased left ventricular mass in a sample of 2426 White individuals.

Background

Methods

Results

Conclusions

Publications

The TRIB3 R84 variant is associated with increased left ventricular mass in a sample of 2426 White individuals.

Similar Datasets

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