Background:
Endothelial nitric oxide synthase (eNOS) plays a major role in the response of antihypercholesterol statin drugs. Genetic polymorphisms in the eNOS gene affect the activity of eNOS and thereby modulate
statin response.
Objectives:
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 a
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.
Renin-Angiotensin System and Nitric Oxide Synthase Gene Polymorphisms in Relation to Stroke
