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ACE 和 AGT 多态性与肢端肥大症患者心血管风险的关联。

Association between ACE and AGT polymorphism and cardiovascular risk in acromegalic patients.

机构信息

Department of Endocrinology and Metabolism, Hacettepe University School of Medicine, Sihhiye, 06100, Ankara, Turkey.

Department of Cardiology, Hacettepe University School of Medicine, Ankara, Turkey.

出版信息

Pituitary. 2017 Oct;20(5):569-577. doi: 10.1007/s11102-017-0819-5.

Abstract

PURPOSE

Whether the renin-angiotensin-aldosterone system plays a role or not in the development of cardiovascular morbidity in acromegaly patients is unknown. The aim of the study was to investigate the association between ACE (I/D) and AGT (M235T) gene polymorphisms and cardiovascular and metabolic disorders in the acromegaly.

METHODS

The study included one hundred and seventeen acromegalic patients (62 F/55 M, age: 50.2 ± 12.3 years) and 106 healthy controls (92 F/14 M, age: 41.4 ± 11.3 years). PCR method was used to evaluate the prevalence of ACE and AGT genotype.

RESULTS

The genotypes of ACE polymorphism in acromegalic patients were distributed as follows; 41.0% (n: 48) for DD, 44.4% (n: 52) for ID and 14.5% (n: 17) for II genotype. The control group had significantly different distribution of the ACE polymorphism [48.1% (n: 51) for DD, 25.5% (n: 27) for ID and 26.4% (n: 28) for II genotype]compared to acromegalic group. Regarding AGT polymorphism, AGT-MT genotype was seen in 88.9% of the acromegalic patients while MM and TT genotype (9.4% and 1.7%, respectively) were present in the rest. The controls had similar distribution of the AGT genotype with the acromegaly group (80.2% MT genotype, 15.1% MM genotype and 4.7% TT genotype). Due to the small number of patients with TT allele (n: 2), T carriers for AGT genotype (AGT-MT+TT) were subgrouped and compared to those with AGT-MM group. ACE-DD, ID and II groups had similar anthropometric measures, blood pressure values and baseline GH and IGF-1 levels. Significantly higher baseline GH levels were found in AGT-MM group compared to T allele carriers [40 (16-60) vs. 12 (5-36) µg/L, p < 0.05]. The compared groups in both polymorphisms had similar fasting plasma glucose levels. Patients with ACE-II genotype had significantly higher HDL-C levels compared to those with ACE-DD and ACE-ID polymorphisms (p < 0.05) whereas there was no significant difference in lipid profile between AGT-MM group and AGT-T allele carriers. Moreover, the compared groups in both polymorphisms had similar distribution of hyperlipidemia, hypertension, impaired glucose metabolism (prediabetes or type 2 diabetes mellitus) and coronary artery disease. In terms of echocardiographic parameters, systolic and diastolic function was similar among the groups in ACE and AGT genotypes. Interestingly, AGT-MM group had higher mitral inflow A values than T allele carriers (0.94 ± 0.46 vs. 0.73 ± 0.20; p = 0.051). No significant difference was observed in LV mass index values in acromegalic patients among the groups in both polymorphisms.

CONCLUSIONS

Both ACE (I/D) and AGT (M235T) gene polymorphisms do not seem to have a significant effect on the development of clinical properties or cardiovascular comordities of acromegalic patients.

摘要

目的

目前尚不清楚肾素-血管紧张素-醛固酮系统(renin-angiotensin-aldosterone system)在肢端肥大症患者心血管发病率的发展中是否起作用。本研究的目的是研究 ACE(I/D)和 AGT(M235T)基因多态性与肢端肥大症患者心血管和代谢紊乱的关系。

方法

该研究纳入了 117 例肢端肥大症患者(62 例女性/55 例男性,年龄:50.2±12.3 岁)和 106 例健康对照者(92 例女性/14 例男性,年龄:41.4±11.3 岁)。采用 PCR 法评估 ACE 和 AGT 基因型的流行情况。

结果

肢端肥大症患者 ACE 多态性的基因型分布如下:41.0%(n:48)为 DD,44.4%(n:52)为 ID,14.5%(n:17)为 II 基因型。对照组 ACE 多态性的分布与肢端肥大症组有显著差异[48.1%(n:51)为 DD,25.5%(n:27)为 ID,26.4%(n:28)为 II 基因型]。关于 AGT 多态性,88.9%的肢端肥大症患者存在 AGT-MT 基因型,而 MM 和 TT 基因型(分别为 9.4%和 1.7%)则较少见。对照组与肢端肥大症组的 AGT 基因型分布相似(80.2%为 MT 基因型,15.1%为 MM 基因型,4.7%为 TT 基因型)。由于 TT 等位基因患者人数较少(n:2),因此将 AGT 基因型的 T 携带者(AGT-MT+TT)分为亚组,并与 AGT-MM 组进行比较。ACE-DD、ID 和 II 组的人体测量指标、血压值和基线 GH 和 IGF-1 水平相似。与 T 等位基因携带者相比,AGT-MM 组的基线 GH 水平显著更高[40(16-60)比 12(5-36)μg/L,p<0.05]。两种多态性的比较组空腹血糖水平相似。与 ACE-DD 和 ACE-ID 多态性相比,ACE-II 基因型患者的 HDL-C 水平显著更高(p<0.05),而 AGT-MM 组与 AGT-T 等位基因携带者的血脂谱无显著差异。此外,两种多态性的比较组在高脂血症、高血压、糖代谢受损(糖尿病前期或 2 型糖尿病)和冠状动脉疾病的分布相似。在超声心动图参数方面,ACE 和 AGT 基因型组的收缩和舒张功能相似。有趣的是,与 T 等位基因携带者相比,AGT-MM 组的二尖瓣血流 A 值更高(0.94±0.46 比 0.73±0.20;p=0.051)。两种多态性的肢端肥大症患者的左心室质量指数值无显著差异。

结论

ACE(I/D)和 AGT(M235T)基因多态性似乎对肢端肥大症患者的临床特征或心血管并发症的发展没有显著影响。

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