Background: Studies have shown a direct association between angiotensin-converting enzyme (ACE) and diabetic
neuropathies. As such, ACE gene polymorphisms could be a risk factor for cardiac autonomic neuropathy (CAN) in
patients with diabetes. The objective of our study was to investigate the association of the ACE I/D gene
polymorphism with the development of CAN in Iraqi patients with type 2 diabetes mellitus (T2DM).
Results: This is a cross-sectional study that included 142 patients with T2DM comprising 62 males and 80 females,
and 100 volunteers served as a healthy control group. Cardiac autonomic functions were tested using four standard
Ewing’s noninvasive tests. Blood samples were taken for genetic evaluation of an ACE gene I/D polymorphism.
Analyzing ACE gene polymorphism revealed that the D allele was far more frequent among patients with diabetes
than healthy control subjects (76.07% vs. 62.67%). The frequency of I/I, I/D, and D/D genotypes in patients with
diabetes was 8.55%, 30.77%, and 60.68%, respectively, compared with 18.67%, 37.33%, and 44%, respectively, in
controls with a significant difference in mutant homozygous genotype. However, there were no significant
differences in these genotypes between patients with and without CAN. Although patients with CAN showed a
much higher frequency of D allele than those without CAN, the difference did not reach significance (p = 0.054).
Conclusion: The DD genotype and D allele of the ACE I/D gene polymorphism can be a risk factor for T2DM, and
the D allele of this polymorphism can even be associated with the development of CAN in these patients.
Keywords: DM, Cardiac autonomic neuropathy, ACE gene polymorphism
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12-June-2020
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