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.