The Influence of Endothelial Nitric Oxide Synthase (eNOS) Genetic Polymorphisms on Cholesterol Blood Levels Among Type 2 Diabetic Patients on Atorvastatin Therapy.


Journal

Endocrine, metabolic & immune disorders drug targets
ISSN: 2212-3873
Titre abrégé: Endocr Metab Immune Disord Drug Targets
Pays: United Arab Emirates
ID NLM: 101269157

Informations de publication

Date de publication:
2021
Historique:
received: 30 01 2020
revised: 30 04 2020
accepted: 08 05 2020
pubmed: 23 6 2020
medline: 27 10 2021
entrez: 23 6 2020
Statut: ppublish

Résumé

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. 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. 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. 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). 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.

Sections du résumé

BACKGROUND 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 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 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 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 CONCLUSIONS
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.

Identifiants

pubmed: 32564765
pii: EMIDDT-EPUB-107521
doi: 10.2174/1871530320666200621174858
doi:

Substances chimiques

Anticholesteremic Agents 0
Cholesterol 97C5T2UQ7J
Atorvastatin A0JWA85V8F
NOS3 protein, human EC 1.14.13.39
Nitric Oxide Synthase Type III EC 1.14.13.39

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

352-359

Informations de copyright

Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

Auteurs

Sarah Abdullah (S)

Department of Pharmacology, Faculty of Medicine, University of Jordan, Amman, Jordan.

Yazun Jarrar (Y)

Department of Pharmaceutical Science, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman, Jordan.

Hussam Alhawari (H)

Department of Internal Medicine, Faculty of Medicine, University of Jordan, Amman, Jordan.

Eyada Abed (E)

Department of Pharmacology, Faculty of Medicine, University of Jordan, Amman, Jordan.

Malek Zihlif (M)

Department of Pharmacology, Faculty of Medicine, University of Jordan, Amman, Jordan.

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Classifications MeSH