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.
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 TRIB3Q84R 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 TRIB3Q84R variant is significantly associated with left ventricular mass in a large sample of White nondiabetic individual of European ancestry.
Entities:
Keywords:
Cardiovascular disease; Genetics; Insulin signaling; Left ventricular mass index; TRIB3 Q84R variant; rs2295490
Authors: F Perticone; R Ceravolo; C Cosco; M Trapasso; A Zingone; P Malatesta; N Perrotti; D Tramontano; P L Mattioli Journal: J Am Coll Cardiol Date: 1997-02 Impact factor: 24.094
Authors: P Verdecchia; G Reboldi; G Schillaci; C Borgioni; A Ciucci; M P Telera; F Santeusanio; C Porcellati; P Brunetti Journal: Circulation Date: 1999-10-26 Impact factor: 29.690
Authors: A Ilercil; R B Devereux; M J Roman; M Paranicas; M J O'grady; T K Welty; D C Robbins; R R Fabsitz; B V Howard; E T Lee Journal: Am Heart J Date: 2001-06 Impact factor: 4.749
Authors: Pim van der Harst; Jessica van Setten; Niek Verweij; Georg Vogler; Lude Franke; Matthew T Maurano; Xinchen Wang; Irene Mateo Leach; Mark Eijgelsheim; Nona Sotoodehnia; Caroline Hayward; Rossella Sorice; Osorio Meirelles; Leo-Pekka Lyytikäinen; Ozren Polašek; Toshiko Tanaka; Dan E Arking; Sheila Ulivi; Stella Trompet; Martina Müller-Nurasyid; Albert V Smith; Marcus Dörr; Kathleen F Kerr; Jared W Magnani; Fabiola Del Greco M; Weihua Zhang; Ilja M Nolte; Claudia T Silva; Sandosh Padmanabhan; Vinicius Tragante; Tõnu Esko; Gonçalo R Abecasis; Michiel E Adriaens; Karl Andersen; Phil Barnett; Joshua C Bis; Rolf Bodmer; Brendan M Buckley; Harry Campbell; Megan V Cannon; Aravinda Chakravarti; Lin Y Chen; Alessandro Delitala; Richard B Devereux; Pieter A Doevendans; Anna F Dominiczak; Luigi Ferrucci; Ian Ford; Christian Gieger; Tamara B Harris; Eric Haugen; Matthias Heinig; Dena G Hernandez; Hans L Hillege; Joel N Hirschhorn; Albert Hofman; Norbert Hubner; Shih-Jen Hwang; Annamaria Iorio; Mika Kähönen; Manolis Kellis; Ivana Kolcic; Ishminder K Kooner; Jaspal S Kooner; Jan A Kors; Edward G Lakatta; Kasper Lage; Lenore J Launer; Daniel Levy; Alicia Lundby; Peter W Macfarlane; Dalit May; Thomas Meitinger; Andres Metspalu; Stefania Nappo; Silvia Naitza; Shane Neph; Alex S Nord; Teresa Nutile; Peter M Okin; Jesper V Olsen; Ben A Oostra; Josef M Penninger; Len A Pennacchio; Tune H Pers; Siegfried Perz; Annette Peters; Yigal M Pinto; Arne Pfeufer; Maria Grazia Pilia; Peter P Pramstaller; Bram P Prins; Olli T Raitakari; Soumya Raychaudhuri; Ken M Rice; Elizabeth J Rossin; Jerome I Rotter; Sebastian Schafer; David Schlessinger; Carsten O Schmidt; Jobanpreet Sehmi; Herman H W Silljé; Gianfranco Sinagra; Moritz F Sinner; Kamil Slowikowski; Elsayed Z Soliman; Timothy D Spector; Wilko Spiering; John A Stamatoyannopoulos; Ronald P Stolk; Konstantin Strauch; Sian-Tsung Tan; Kirill V Tarasov; Bosco Trinh; Andre G Uitterlinden; Malou van den Boogaard; Cornelia M van Duijn; Wiek H van Gilst; Jorma S Viikari; Peter M Visscher; Veronique Vitart; Uwe Völker; Melanie Waldenberger; Christian X Weichenberger; Harm-Jan Westra; Cisca Wijmenga; Bruce H Wolffenbuttel; Jian Yang; Connie R Bezzina; Patricia B Munroe; Harold Snieder; Alan F Wright; Igor Rudan; Laurie A Boyer; Folkert W Asselbergs; Dirk J van Veldhuisen; Bruno H Stricker; Bruce M Psaty; Marina Ciullo; Serena Sanna; Terho Lehtimäki; James F Wilson; Stefania Bandinelli; Alvaro Alonso; Paolo Gasparini; J Wouter Jukema; Stefan Kääb; Vilmundur Gudnason; Stephan B Felix; Susan R Heckbert; Rudolf A de Boer; Christopher Newton-Cheh; Andrew A Hicks; John C Chambers; Yalda Jamshidi; Axel Visel; Vincent M Christoffels; Aaron Isaacs; Nilesh J Samani; Paul I W de Bakker Journal: J Am Coll Cardiol Date: 2016-09-27 Impact factor: 24.094
Authors: Martin K Rutter; Helen Parise; Emelia J Benjamin; Daniel Levy; Martin G Larson; James B Meigs; Richard W Nesto; Peter W F Wilson; Ramachandran S Vasan Journal: Circulation Date: 2003-01-28 Impact factor: 29.690