内皮型一氧化氮合酶（eNOS）基因多态性对阿托伐他汀治疗的 2 型糖尿病患者胆固醇水平的影响。
The Influence of Endothelial Nitric Oxide Synthase (eNOS) Genetic Polymorphisms on Cholesterol Blood Levels Among Type 2 Diabetic Patients on Atorvastatin Therapy.
机构信息
Department of Pharmacology, Faculty of Medicine, University of Jordan, Amman, Jordan.
Department of Pharmaceutical Science, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman, Jordan.
出版信息
Endocr Metab Immune Disord Drug Targets. 2021;21(2):352-359. doi: 10.2174/1871530320666200621174858.
BACKGROUND
Endothelial nitric oxide synthase (eNOS) plays a major role in the response of anti-hypercholesterol statin drugs. Genetic polymorphisms in the eNOS gene affect the activity of eNOS thereby modulating the statin response.
OBJECTIVE
This study investigated the influence of major functional eNOS gene polymorphisms (rs2070744, rs1799983, and rs61722009) on the lipid profile of type 2 diabetes mellitus (T2DM) Jordanian patients treated with atorvastatin.
METHODS
The sample comprised 103 T2DM patients who attended the diabetes clinic of Jordan University Hospital. The T2DM patients had regularly been taking 20 mg atorvastatin. The atorvastatin response was calculated by measuring the lipid profile before and after three months of atorvastatin treatment. The eNOS genotypes of the subjects were analyzed using polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) assay.
RESULTS
No significant association was found between eNOS genetic polymorphisms and the response to atorvastatin (ANOVA, p > 0.05). In addition, no significant difference in the frequency of eNOS genotypes was found between T2DM patients and healthy subjects. However, patients with eNOS rs1799983, 4a/4a, and rs61722009 G/G genotypes showed significantly lower levels of baseline total cholesterol (TC) and low density lipoprotein (LDL) than did patients carrying the rs1799983 4b/4b or rs61722009 T/T genotype (p < 0.05). The eNOS rs1799983 and rs61722009 polymorphisms were in complete linkage disequilibrium (D' = 1).
CONCLUSION
Although no association was found between eNOS genetic polymorphisms and atorvastatin response, there was a significant association between the rs1799983 and rs61722009 genotypes and baselines levels of TC and LDL in Jordanian T2DM patients. These genetic variants affect cholesterol levels and may play a role in the susceptibility to cardiovascular diseases in T2DM patients. Further studies are needed to validate these findings.
背景
内皮型一氧化氮合酶（eNOS）在抗高胆固醇他汀类药物的反应中起着重要作用。eNOS 基因的遗传多态性影响 eNOS 的活性，从而调节他汀类药物的反应。
目的
本研究旨在探讨主要功能性 eNOS 基因多态性（rs2070744、rs1799983 和 rs61722009）对接受阿托伐他汀治疗的 2 型糖尿病（T2DM）约旦患者血脂谱的影响。
方法
该样本包括 103 名在约旦大学医院糖尿病诊所就诊的 T2DM 患者。这些 T2DM 患者定期服用 20mg 阿托伐他汀。通过测量阿托伐他汀治疗三个月前后的血脂谱来计算阿托伐他汀的反应。使用聚合酶链反应（PCR）后限制性片段长度多态性（RFLP）分析来分析受试者的 eNOS 基因型。
结果
eNOS 遗传多态性与阿托伐他汀的反应之间无显著相关性（方差分析，p>0.05）。此外，T2DM 患者与健康受试者之间的 eNOS 基因型频率无显著差异。然而，携带 eNOS rs1799983、4a/4a 和 rs61722009 G/G 基因型的患者总胆固醇（TC）和低密度脂蛋白（LDL）基线水平明显低于携带 rs1799983 4b/4b 或 rs61722009 T/T 基因型的患者（p<0.05）。eNOS rs1799983 和 rs61722009 多态性完全连锁不平衡（D'=1）。
结论
尽管 eNOS 遗传多态性与阿托伐他汀反应之间无关联，但在约旦 2 型糖尿病患者中，rs1799983 和 rs61722009 基因型与 TC 和 LDL 基线水平之间存在显著关联。这些遗传变异影响胆固醇水平，可能在 2 型糖尿病患者患心血管疾病的易感性中起作用。需要进一步的研究来验证这些发现。
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