摘要
为了探讨淀粉样前体蛋白(amyloid precursor protein, APP)基因甲基化与冠状动脉粥样硬化性心脏病(coronary heart disease, CHD)之间的关系,采用甲基化特异性实时定量聚合酶链反应(quantitative methylation-specific PCR, qMSP)检测538名CHD患者及453名正常对照者的APP甲基化修饰水平。结果显示:CHD组的年龄、男性人数、吸烟及糖尿病患者人数均高于对照组(年龄, P=8.0E-08;男性人数, P=7.0E-07;吸烟, P=0.001;糖尿病,P=0.019)。CHD组患者白蛋白水平显著低于对照组(P=0.001),而AST、ALP及γ-GT的水平在CHD组中显著高于对照组(AST, P=3.0E-04; ALP, P=0.001;γ-GT, P=0.018)。在总体样本及男性样本中, APP基因甲基化水平在CHD组显著高于对照组(总体, P=0.026;男性, P=0.025)。在非吸烟CHD患者中, APP基因甲基化水平与狭窄程度呈正比(r=0.076, P=0.046)。在总体CHD伴高血压患者及男性CHD伴高血压患者中, APP基因甲基化水平和狭窄程度呈正比(总体, r=0.096, P=0.029;男性, r=0.135, P=0.019)。年龄分层分析后发现,在年龄≥63岁的男性CHD伴高血压患者中, APP基因甲基化水平与狭窄程度呈正比(r=0.219, P=0.020)。在年龄<63岁的不吸烟或非高血压CHD患者中, APP基因甲基化水平与狭窄程度呈负相关(不吸烟, r=-0.223, P=0.008;非高血压,r=-0.216, P=0.010)。在男性CHD患者中, APP基因甲基化水平与年龄呈正相关(r=0.163, P=0.001)。在女性CHD患者中, APP基因甲基化水平与年龄呈负相关(r=-0.192, P=0.015)。在男性正常对照组中, APP基因甲基化水平与年龄呈负相关(r=-0.203, P=0.001)。在女性正常对照组中, APP基因甲基化水平与ApoB、白蛋白及ALT水平呈负相关(r=-0.160, P=0.028; r=-0.151, P=0.036; r=-0.163, P=0.024)。在正常对照组中, APP基因甲基化水平与Lp(a)水平呈正相关(r=0.108, P=0.031)。以上结果初步表明APP基因甲基化水平增高可能和男性CHD患病风险有关。
To investigate the relationship between methylation of amyloid precursor protein(APP) gene and coronary heart disease(CHD), the APP methylation levels of 538 CHD patients and 453 normal controls were detected using the quantitative methylation-specific PCR(qMSP). The results showed that the age, the num-bers of males, smokers and diabetic patients were significantly higher in CHD patients than in controls(age,P =8.0 E-08; males, P =7.0 E-07; smokers, P =0.001; diabetes, P =0.019). Albumin levels were significantly lower in the CHD group than in the control group(P=0.001), while AST, ALP, and γ-GT levels were significantly higher in the CHD group than in control group(AST, P=3.0 E-04; ALP, P=0.001; γ-GT, P=0.018). In both total and male samples, the methylation levels of the APP gene were found to be significantly higher in the CHD group than in the control group(total samples, P=0.026; males, P=0.025). In non-smoking CHD patients, the APP methylation level was positively related to the degree of stenosis(r=0.076, P=0.046). In both total CHD patients with hypertension and CHD male patients with hypertension, APP methylation levels were found to be positively related to the degree of stenosis(total samples, r=0.096, P=0.029; males, r=0.135, P=0.019). After age stratification, it was found that the APP methylation level was positively related to stenosis in CHD male patients with hypertension aged ≥63 years(r=0.219, P=0.020). In non-smoking or non-hypertensive CHD patients aged <63 years, APP methylation levels were found to be negatively correlated with stenosis(non-smoking, r=-0.223, P=0.008; non-hypertension, r=-0.216, P=0.010). In CHD male patients, a positive correlation was found between the APP methylation level and the age(r=0.163, P=0.001). In CHD female patients, an inverse correlation was observed between the APP methylation level and the age(r=-0.192, P=0.015).In normal male controls, the APP methylation level was inversely correlated with the age(r=-0.203, P=0.001).In normal female controls, APP methylation level was inversely correlated with ApoB, albumin and ALT levels(r =-0.160, P =0.028; r =-0.151, P =0.036; r =-0.163, P =0.024, respectively). In the normal group, the APP methylation level was positively correlated with Lp(a) level(r=0.108, P=0.031). In conclusion, the above results showed that the increased methylation level of APP gene might be related to the risk of CHD in males.
引文
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