TY - JOUR
T1 - Variants of trophic factors and expression of cardiac hypertrophy in patients with hypertrophic cardiomyopathy
AU - Patel, Rajnikant
AU - Lim, Do Sun
AU - Reddy, Deepa
AU - Nagueh, Sherif
AU - Lutucuta, Sylvia
AU - Sole, Michael J.
AU - Zoghbi, William A.
AU - Quiñones, Miguel A.
AU - Roberts, Robert
AU - Marian, Ali J.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2000
Y1 - 2000
N2 - Patients with hypertrophic cardiomyopathy (HCM) exhibit variable expression of left ventricular hypertrophy (LVH), a major determinant of mortality and morbidity, which is partly due to the diversity of causal mutations, genetic background (modifier genes), and probably environmental factors. We determined association of functional variants of tumor necrosis factor (TNF)-α, interleukin-6 (IL6), insulin-like growth factor-2 (IGF2), transforming growth factor-β1 (TGFB1), and aldosterone synthase (CYP11B2) genes, all previously implicated in cardiac hypertrophy, with the severity of LVH in patients with HCM. TWo-dimensional echocardiography was performed and demographic variables were recorded in 142 genetically independent patients. Indices of LVH including interventricular septal thickness (IVST), left ventricular mass index (LVMI), and LVH score were measured/calculated. TNF-α - 308G/A, IL6 - 174G/C, IGF2 820G/A, TGFB1 - 509C/T, and CYP11B2 - 344T/C genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Genotypes were identified by the presence of specific electrophoretic patterns and their distributions were according to the Hardy-Weinberg equilibrium. Demographic variables were not significantly different among the genotypes. Subjects with the AA genotype of TNF-α (n = 8) were approximately 13 years younger at the time of clinical diagnosis. Despite a younger age, they had a greater mean LVMI than those with the GG (n=94) or GA (n=33) genotypes (191.8 ± 59.5 v 139.1 ± 47.3 v 132.1 ± 34.3, respectively, P = 0.004). TNF-α - 308G/A genotypes accounted for 6.0% of variability of LVMI (P=0.002). Mean IVST, LVEDD, and LVH score were not significantly different. Variants of IL6, IGF2, TGFB1, and CYP11B2 were not associated with indices of LVH. The uncommon allele of TNF-α -308G/A polymorphism, known to produce more TNF-α, was associated with greater LVMI and clinical diagnosis at a younger age in patients with HCM. Functional variants of other trophic factors, previously implicated in cardiac hypertrophy, were not associated with the indices of LVH. These results suggest that TNF-α is a modifier gene for HCM.
AB - Patients with hypertrophic cardiomyopathy (HCM) exhibit variable expression of left ventricular hypertrophy (LVH), a major determinant of mortality and morbidity, which is partly due to the diversity of causal mutations, genetic background (modifier genes), and probably environmental factors. We determined association of functional variants of tumor necrosis factor (TNF)-α, interleukin-6 (IL6), insulin-like growth factor-2 (IGF2), transforming growth factor-β1 (TGFB1), and aldosterone synthase (CYP11B2) genes, all previously implicated in cardiac hypertrophy, with the severity of LVH in patients with HCM. TWo-dimensional echocardiography was performed and demographic variables were recorded in 142 genetically independent patients. Indices of LVH including interventricular septal thickness (IVST), left ventricular mass index (LVMI), and LVH score were measured/calculated. TNF-α - 308G/A, IL6 - 174G/C, IGF2 820G/A, TGFB1 - 509C/T, and CYP11B2 - 344T/C genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Genotypes were identified by the presence of specific electrophoretic patterns and their distributions were according to the Hardy-Weinberg equilibrium. Demographic variables were not significantly different among the genotypes. Subjects with the AA genotype of TNF-α (n = 8) were approximately 13 years younger at the time of clinical diagnosis. Despite a younger age, they had a greater mean LVMI than those with the GG (n=94) or GA (n=33) genotypes (191.8 ± 59.5 v 139.1 ± 47.3 v 132.1 ± 34.3, respectively, P = 0.004). TNF-α - 308G/A genotypes accounted for 6.0% of variability of LVMI (P=0.002). Mean IVST, LVEDD, and LVH score were not significantly different. Variants of IL6, IGF2, TGFB1, and CYP11B2 were not associated with indices of LVH. The uncommon allele of TNF-α -308G/A polymorphism, known to produce more TNF-α, was associated with greater LVMI and clinical diagnosis at a younger age in patients with HCM. Functional variants of other trophic factors, previously implicated in cardiac hypertrophy, were not associated with the indices of LVH. These results suggest that TNF-α is a modifier gene for HCM.
KW - Cytokines
KW - Genes
KW - Growth factors
KW - Hypertrophy
KW - Polymorphism
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U2 - 10.1006/jmcc.2000.1267
DO - 10.1006/jmcc.2000.1267
M3 - Article
C2 - 11113012
AN - SCOPUS:0034502439
SN - 0022-2828
VL - 32
SP - 2369
EP - 2377
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
IS - 12
ER -