Role of candidate modifier genes on the phenotypic expression of hypertrophy in patients with hypertrophic cardiomyopathy.
Role of candidate modifier genes on the phenotypic expression of hypertrophy in patients with hypertrophic cardiomyopathy.
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发表时间：
1997-12
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通讯作者：
R. Brugada;Winifred Kelsey;M. Lechin;Guiling Zhao;Q. Yu;W. Zoghbi;M. Quiñones;E. Elstein;A. Omran;H. Rakowski;D. Wigle;C. Liew;M. Sole;R. Roberts;A. Marian
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作者：
R. Brugada;Winifred Kelsey;M. Lechin;Guiling Zhao;Q. Yu;W. Zoghbi;M. Quiñones;E. Elstein;A. Omran;H. Rakowski;D. Wigle;C. Liew;M. Sole;R. Roberts;A. Marian
肥厚型心肌病（HCM）患者左室肥厚（LVH）的表型表达是可变的。这种表型变异性不能完全由负责的突变或其他已知因素解释。最近的数据表明修饰基因和环境因素的作用。我们研究了3个潜在的修饰基因的作用，即，血管紧张素原（AGT）、血管紧张素II受体1a（AT 1a）和内皮素-1（END 1）对肥厚型心肌病（HCM）患者LVH表型表达的影响。方法研究人群包括108例遗传独立的HCM患者。根据已发表的方案测定左心室质量指数（LVMI）和LVH评分。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）或突变特异性PCR（MS-PCR）检测AGT（M235 T、T174 M和G-6A）、AT 1a和END 1基因型。结果男性患者的平均LVMI和LVH评分高于女性患者（分别为146.0 ± 33.5 vs 129.4 ± 33.6，p = 0.01和6.0 vs 5.0，p = 0.010）。性别对LVMI和LVH评分的影响分别为4.8%和5.4%。END 1基因型也对LVH评分有显著影响，占其变异性的2.9%（p = 0.042）。与GG基因型患者相比，AA和AG基因型患者的中位LVH评分更高（7.0 vs 5.0，p = 0.034）。AGT和AT 1基因型对LVH的表达无显著影响。在多变量回归分析中，END 1和性别占LVH评分变异性的7.3%（p = 0.007）。结论：我们的研究结果表明，性别和END 1基因修饰肥厚型心肌病患者肥大的表型表达。
BACKGROUND The phenotypic expression of left ventricular hypertrophy (LVH) in patients with hypertrophic cardiomyopathy (HCM) is variable. This phenotypic variability is not completely explained by the responsible mutations or other known factors. Recent data denote a role for the modifier genes and environmental factors. We studied the role of 3 potential modifier genes, i.e., angiotensinogen (AGT), angiotensin II receptor 1a (AT1a), and endothelin-1 (END1) on the phenotypic expression of LVH in patients with hypertrophic cardiomyopathy (HCM). METHODS The study population was comprised of 108 genetically independent patients with HCM. Left ventricular mass index (LVMI) and LVH score were determined per published protocols. The genotypes of AGT (M235T, T174M, and G-6A), AT1a, and END1 were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or mutation-specific PCR (MS-PCR). RESULTS Male patients had higher mean LVMI and LVH score than female patients (146.0 +/- 33.5 vs 129.4 +/- 33.6, p = 0.01 and 6.0 vs 5.0, p = 0.010, respectively). Gender accounted for 4.8% and 5.4% of the variability of LVMI and LVH score, respectively. The END1 genotypes also had a significant influence on LVH scores accounting for 2.9% of their variability (p = 0.042). The median LVH score was greater in patients with the AA and AG genotypes, as compared to patients with the GG genotype (7.0 vs 5.0, p = 0.034). Neither the AGT nor the AT1 genotypes had a significant influence on the expression of LVH. In multivariate regression analysis, END1 and gender accounted for 7.3% of the variability of the LVH score (p = 0.007). CONCLUSIONS Our results show that gender and the END1 gene modify the phenotypic expression of hypertrophy in patients with HCM.