儿童阻塞性睡眠呼吸暂停综合征ACE基因多态性的临床研究
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摘要
目的:研究血管紧张素转换酶(ACE)基因多态性及血清ACE水平和血管紧张素Ⅱ(AngⅡ)等血管活性物质水平在儿童阻塞性睡眠呼吸暂停综合征(OSAS)发病中的作用,为判断儿童OSAS病情严重程度、预后及疗效提供遗传与血液生化的依据。
方法:应用聚合酶链反应对124例OSAS患儿及100例正常对照组儿童ACE基因插入/缺失(I/D)多态性进行检测,同时用酶动力学法测定其血清ACE水平,应用酶法或免疫比浊法测定血脂等项目,应用放射免疫法测定124例OSAS患儿及30例正常对照组儿童血浆Ang Ⅱ、内皮素-1(ET-1)含量,比较不同基因型患者间及与正常儿童问血清ACE、Ang Ⅱ、ET-1含量及血脂等水平有无差别。
结果:
1、OSAS患儿Ⅱ、ID、DD基因型患者血清ACE水平分别为(35.5±11.1)U/L,(46.0±15.2)U/L和(52.1±18.9)U/L;组间差异有统计学意义(P<0.01),经两两比较Ⅱ型与DD型及ID型血清ACE水平差异均有统计学意义(P=0.000,0.007),DD型与ID型比较差异无统计学意义(P=0.213);OSAS患儿三组基因型血管紧张素Ⅱ水平分别为(81.9±20.4)pg/ml,(88.7±32.7)pg/ml和(84.1±23.2)pg/ml,三者差别无统计学意义;DD基因型血清ACE水平最高,但ACE基因型对AngⅡ水平无影响。ET-1及血脂水平各基因型间无差异。
2、将OSAS患儿多导睡眠图(PSG)相关参数分别与ACE基因型、血清ACE水平、血脂、血常规、ET-1及AngⅡ结果进行多元线性回归分析,结果显示OSAS患儿PSG结果与ACE基因型、血清ACE水平、血脂、血常规、ET-1等指标间无相关性,仅有AngⅡ浓度与最低血氧饱和度(SaO_2%)相关,相关系数R=0.300,确定系数R~2=0.092,回归方程为:8aO_2%=84.756-2.35×(AngⅡ),对回归系数进行t检验,t=-2.203,P=0.032。将可能影响患者AngⅡ水平的因素进行多元线性回归分析,性别和年龄进入方程,ACE基因型及血清ACE水平不是血浆AngⅡ浓度的影响因素。
Objective: To study the feature of the polymorphism of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) and the level of plasma angiotensin Ⅱ (AngⅡ) , endothelin-1 (ET-1) and lipids in children patients with obstructive sleep apnea-syndrome (OSAS) and to discuss their clinical significance.Methods: The genotype was determined by polymerase chain reaction (PCR) in the124 children patients with OSAS and 100 healthy children control. The levels of serum ACE by enzyme kinetics and the lipids by enzyme method or immunoturbidimetric assay were also assessed in the 124 children patients with OSAS and 100 healthy children control; The levels of plasma ET-1 and Angll by radio-immunity assay (RIA) were measured in the 124 children patients with OSAS and 30 healthy children control. To compare the different between the children patients with OSAS and healthy children control.Result: 1. A marked difference in the serum ACE levels was observed among the 3 genotypes (DD, Ⅱ and ID). The mean levels of serum ACE in DD genotype class were the highest [DD: (52.1 ± 18.9) U/L, II: (35.5±11.1) U/L, ID: (46.0±15.2) U/L; P<0.01, DD Vs Ⅱ, P=0.000; ID Vs Ⅱ, P= 0.007;DD Vs ID, P=0.213]. The mean plasma AngⅡ levels in Ⅱ, ID and DD allele were (81.9±20.4) pg/ml, ( 88.7 ± 32.7) pg/ml and (84.1 ±23.2) pg/ml respectively, with no differences among them. The mean levels of ET-1 and lipids among the ACE genotypes in the OSAS patients have no difference.2. Multifactor linear regression demonstrated that there was no correlation between the polysomngram (PSG) result and the ACE genotypes, the levels of serum ACE, lipids, plasma ET-1 in the children patients with OSAS. There were only positive correlation between the concentration of Angll and the lowest oxygen saturation (SaO_2%) in all the 124 children patients with OSAS. Multifactor linear regression
demonstrated that there were positive correlations between the concentration of Angll and the age or sex. The ACE genotypes and the levels of the serum ACE did not affect the concentration of plasma Angll.3. The frequency of DD genotype and D allele were significantly higher in the OSAS patients than those in the healthy control (x2=29.701, -￡=22.611,respectively). There were significantly different in lipids, RBC and MCHC between the 124 children patients with OSAS and the 100 healthy children control. The RBC level was significantly higher and the MCHC level was significantly lower in the OSAS patients than those in the healthy control. Plasma levels of ET-1 and Angll were significantly higher in the 124 children patients with OSAS than those in the 30 healthy children control (/><0.05) .Conclusion: 1. The frequency of DD genotype and D allele were significantlyhigher in the OSAS patients than those in the healthy control. In the DD genotype serum ACE level was greater than it in the ID genotype and II genotype. The polymorphism of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) ACE genotype may be correlated with OSAS in children patients.2. The ACE genotypes and the levels of the serum ACE did not affect the concentration of plasma Angll. Plasma levels of ET-1 and Angll were significantly higher in the 124 children patients with OSAS than those in the 30 healthy children control. There was no correlation between the PSG result and the ACE genotypes, the levels of serum ACE, lipids, plasma ET-1 in the children patients with OSAS. There were only positive correlation between the concentration of Angll and the lowest oxygen saturation (SaO2%) in all the 124 children patients with OSAS.3. The levels of lipids in OSAS children patients were significantly lower than those in healthy control. The RBC level was significantly higher in the OSAS patients than it in the healthy control. The OSAS children patients may be easy to accompany hypercythemia.
方法:应用聚合酶链反应对124例OSAS患儿及100例正常对照组儿童ACE基因插入/缺失(I/D)多态性进行检测,同时用酶动力学法测定其血清ACE水平,应用酶法或免疫比浊法测定血脂等项目,应用放射免疫法测定124例OSAS患儿及30例正常对照组儿童血浆Ang Ⅱ、内皮素-1(ET-1)含量,比较不同基因型患者间及与正常儿童问血清ACE、Ang Ⅱ、ET-1含量及血脂等水平有无差别。
结果:
1、OSAS患儿Ⅱ、ID、DD基因型患者血清ACE水平分别为(35.5±11.1)U/L,(46.0±15.2)U/L和(52.1±18.9)U/L;组间差异有统计学意义(P<0.01),经两两比较Ⅱ型与DD型及ID型血清ACE水平差异均有统计学意义(P=0.000,0.007),DD型与ID型比较差异无统计学意义(P=0.213);OSAS患儿三组基因型血管紧张素Ⅱ水平分别为(81.9±20.4)pg/ml,(88.7±32.7)pg/ml和(84.1±23.2)pg/ml,三者差别无统计学意义;DD基因型血清ACE水平最高,但ACE基因型对AngⅡ水平无影响。ET-1及血脂水平各基因型间无差异。
2、将OSAS患儿多导睡眠图(PSG)相关参数分别与ACE基因型、血清ACE水平、血脂、血常规、ET-1及AngⅡ结果进行多元线性回归分析,结果显示OSAS患儿PSG结果与ACE基因型、血清ACE水平、血脂、血常规、ET-1等指标间无相关性,仅有AngⅡ浓度与最低血氧饱和度(SaO_2%)相关,相关系数R=0.300,确定系数R~2=0.092,回归方程为:8aO_2%=84.756-2.35×(AngⅡ),对回归系数进行t检验,t=-2.203,P=0.032。将可能影响患者AngⅡ水平的因素进行多元线性回归分析,性别和年龄进入方程,ACE基因型及血清ACE水平不是血浆AngⅡ浓度的影响因素。
Objective: To study the feature of the polymorphism of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) and the level of plasma angiotensin Ⅱ (AngⅡ) , endothelin-1 (ET-1) and lipids in children patients with obstructive sleep apnea-syndrome (OSAS) and to discuss their clinical significance.Methods: The genotype was determined by polymerase chain reaction (PCR) in the124 children patients with OSAS and 100 healthy children control. The levels of serum ACE by enzyme kinetics and the lipids by enzyme method or immunoturbidimetric assay were also assessed in the 124 children patients with OSAS and 100 healthy children control; The levels of plasma ET-1 and Angll by radio-immunity assay (RIA) were measured in the 124 children patients with OSAS and 30 healthy children control. To compare the different between the children patients with OSAS and healthy children control.Result: 1. A marked difference in the serum ACE levels was observed among the 3 genotypes (DD, Ⅱ and ID). The mean levels of serum ACE in DD genotype class were the highest [DD: (52.1 ± 18.9) U/L, II: (35.5±11.1) U/L, ID: (46.0±15.2) U/L; P<0.01, DD Vs Ⅱ, P=0.000; ID Vs Ⅱ, P= 0.007;DD Vs ID, P=0.213]. The mean plasma AngⅡ levels in Ⅱ, ID and DD allele were (81.9±20.4) pg/ml, ( 88.7 ± 32.7) pg/ml and (84.1 ±23.2) pg/ml respectively, with no differences among them. The mean levels of ET-1 and lipids among the ACE genotypes in the OSAS patients have no difference.2. Multifactor linear regression demonstrated that there was no correlation between the polysomngram (PSG) result and the ACE genotypes, the levels of serum ACE, lipids, plasma ET-1 in the children patients with OSAS. There were only positive correlation between the concentration of Angll and the lowest oxygen saturation (SaO_2%) in all the 124 children patients with OSAS. Multifactor linear regression
demonstrated that there were positive correlations between the concentration of Angll and the age or sex. The ACE genotypes and the levels of the serum ACE did not affect the concentration of plasma Angll.3. The frequency of DD genotype and D allele were significantly higher in the OSAS patients than those in the healthy control (x2=29.701, -￡=22.611,respectively). There were significantly different in lipids, RBC and MCHC between the 124 children patients with OSAS and the 100 healthy children control. The RBC level was significantly higher and the MCHC level was significantly lower in the OSAS patients than those in the healthy control. Plasma levels of ET-1 and Angll were significantly higher in the 124 children patients with OSAS than those in the 30 healthy children control (/><0.05) .Conclusion: 1. The frequency of DD genotype and D allele were significantlyhigher in the OSAS patients than those in the healthy control. In the DD genotype serum ACE level was greater than it in the ID genotype and II genotype. The polymorphism of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) ACE genotype may be correlated with OSAS in children patients.2. The ACE genotypes and the levels of the serum ACE did not affect the concentration of plasma Angll. Plasma levels of ET-1 and Angll were significantly higher in the 124 children patients with OSAS than those in the 30 healthy children control. There was no correlation between the PSG result and the ACE genotypes, the levels of serum ACE, lipids, plasma ET-1 in the children patients with OSAS. There were only positive correlation between the concentration of Angll and the lowest oxygen saturation (SaO2%) in all the 124 children patients with OSAS.3. The levels of lipids in OSAS children patients were significantly lower than those in healthy control. The RBC level was significantly higher in the OSAS patients than it in the healthy control. The OSAS children patients may be easy to accompany hypercythemia.
引文
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