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

  • Mannino, Gaia Chiara1
  • Averta, Carolina1
  • Fiorentino, Teresa Vanessa1
  • Succurro, Elena1
  • Spiga, Rosangela1
  • Mancuso, Elettra1
  • Miceli, Sofia1
  • Perticone, Maria1
  • Sciacqua, Angela1
  • Andreozzi, Francesco1
  • Sesti, Giorgio2
  • 1 University “Magna Graecia” of Catanzaro, Viale Europa, Catanzaro, 88100, Italy , Catanzaro (Italy)
  • 2 Sapienza University of Rome, Viale Regina Elena, 324, Rome, 00161, Italy , Rome (Italy)
Published Article
Cardiovascular Diabetology
Springer (Biomed Central Ltd.)
Publication Date
May 29, 2021
DOI: 10.1186/s12933-021-01308-4
Springer Nature


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

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