候选修饰基因在肥厚型心肌病患者肥厚表型表达中的作用。

Role of candidate modifier genes on the phenotypic expression of hypertrophy in patients with hypertrophic cardiomyopathy.

作者信息

Brugada R, Kelsey W, Lechin M, Zhao G, Yu Q T, Zoghbi W, Quinones M, Elstein E, Omran A, Rakowski H, Wigle D, Liew C C, Sole M, Roberts R, Marian A J

机构信息

Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.

出版信息

J Investig Med. 1997 Dec;45(9):542-51.

PMID:9444881

Abstract

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.

摘要

背景

肥厚型心肌病（HCM）患者左心室肥厚（LVH）的表型表达存在差异。这种表型差异不能完全由相关突变或其他已知因素来解释。近期数据表明修饰基因和环境因素发挥了作用。我们研究了3种潜在修饰基因，即血管紧张素原（AGT）、血管紧张素II受体1a（AT1a）和内皮素-1（END1）对肥厚型心肌病（HCM）患者LVH表型表达的作用。

方法

研究人群包括108例基因独立的HCM患者。根据已发表的方案确定左心室质量指数（LVMI）和LVH评分。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）或突变特异性PCR（MS-PCR）确定AGT（M235T、T174M和G-6A）、AT1a和END1的基因型。

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；6.0 vs 5.0，p = 0.010）。性别分别占LVMI和LVH评分变异性的4.8%和5.4%。END1基因型对LVH评分也有显著影响，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LVH评分中位数更高（7.0 vs 5.0，p = 0.034）。AGT和AT1基因型对LVH表达均无显著影响。在多变量回归分析中，END1和性别占LVH评分变异性的7.3%（p = 0.007）。