血管紧张素原基因M235T多态性与肥厚型心肌病的关系

Association of angiotensinogen gene M235T variant with hypertrophic cardiomyopathy

目的 探讨血管紧张素原 ( angiotensinogen,AGT)基因 M2 35 T变异与肥厚型心肌病( hypertrophic cardiomyopathy,HCM)的关系。方法 对 72例 HCM患者与 80名正常对照者进行病例 -对照研究。采用聚合酶链反应与限制性片段长度多态性技术检测 AGT基因 M2 35 T变异。同时通过 M型二维超声心动图分别测量室间隔、左室后壁和心尖部心肌厚度。结果 ( 1)经 PCR扩增及 Tth111 酶切 ,AGT基因型有 3种形式 :MM、TT与 MT基因型。两组 AGT基因型的分布均符合 Hardy- Weinberg平衡。 ( 2 )AGT基因 M2 35 T基因型在 HCM组与对照组的分布差异有显著性 ( χ2 =6 .0 90 ,P<0 .0 5 )。HCM组 TT基因型与 T2 35等位基因的频率均高于对照组 ( TT基因型 :0 .6 3vs0 .4 5 ,OR=2 .0 37,95 % CI:1.0 6 4～7.899,P<0 .0 5 ;T2 35等位基因 :0 .78vs0 .6 4 ,OR=1.990 ,95 % CI:1.197～ 3.30 8,P<0 .0 1)。 ( 3) HCM组TT基因型患者左室壁最厚处平均厚度明显大于 MM、MT基因型患者 [( 19.1± 4 .8) mm vs( 15 .3± 2 .6 )mm与 ( 16 .2± 5 .1) mm,F=4 .2 6 1,P<0 .0 5 ]。结论 AGT基因 M2 35 T变异与 HCM的发病显著相关 ,TT基因型或 T2 35等位基因可能是参与

Objective To evaluate the influence of the angiotensinogen(AGT) gene M235T variant on the prevalence and severity of hypertrophic cardiomyopathy(HCM). Methods The authors conducted a case-control study on 152 subjects, including 72 HCM patients and 80 normal controls. Polymerase chain reaction(PCR)combined with restriction fragment length polymorphism(RFLP)was used to detect the M235T variant of AGT gene. Interventricular septum thickness, left ventricular posterior wall thickness and apical wall thickness were measured by means of M-mode echocardiography under two-dimensional guidance in the parasternal long-axis plane and apical two- and four-chamber views. Results (1)The genotype distributions of AGT gene in both groups were in agreement with Hardy-Weinberg equilibrium. (2)The genotype distributions of the M235T variant differed significantly in HCM patients and controls (χ 2= 6.090, P <0.05). The frequencies of TT genotype and T235 allele in HCM patients were higher than did the patients in controls(TT genotype:0.63 vs 0.45,OR=2.037,95%CI:1.064-7.899, P <0.05;T235 allele:0.78 vs 0.64,OR=1.990,95%CI:1.197-3.308, P <0.01). (3)The patients with the TT genotype had significantly greater mean left ventricular maximal wall thickness than did the patients with the MM and MT genotypes [(19.1±4.8)mm vs (15.3±2.6)mm and(16.2±5.1)mm, F =4.261, P <0.05]. Conclusion The variant M235T of the AGT gene is significantly associated with HCM in this population. The genotype TT or allele T might be a genetic risk factor for the development and extent of hypertrophy in HCM patients.