Relationship between Angiotensin-Converting Enzyme Gene Polymorphism and Insulin Resistance in Never-Treated Hypertensive Patients

Abstract

The association between angiotensin-converting enzyme (ACE) gene polymorphism and insulin resistance (IR) in hypertensive subjects remains controversial. Thus, we evaluated the possible association between IR and ACE gene polymorphism in a group of hypertensive, never-treated patients compared with that in a normotensive control group. We enrolled 200 (114 men and 86 women; age, 45.5 +/- 4.7 yr) hypertensive patients and 96 (54 men and 42 women; age, 44.0 +/- 4.7 yr) normotensive subjects. A double PCR assay was used to identify ACE genotypes. We determined fasting glucose and insulin by the glucose oxidase method and using a standard RIA technique. IR was estimated using the homeostasis model assessment (HOMA(IR)). Both fasting glucose (5.0 +/- 0.3 vs. 4.7 +/- 0.3 mmol/L; P < 0.0001), insulin levels (12.3 +/- 4.7 vs. 4.9 +/- 1.5 muU/mL; P < 0.0001), and HOMA(IR) (2.7 +/- 1.1 vs. 1.1 +/- 0.3; P < 0.0001) were significantly higher in hypertensive patients than in the normotensive control group. When we subdivided hypertensive patients according to ACE genotype, we observed that fasting insulin and HOMA(IR) were 16.3 +/- 3.3 and 3.6 +/- 0.8 in the DD genotype, 9.4 +/- 3.1 and 2.1 +/- 0.7 in the ID genotype, and 8.3 +/- 2.8 and 1.9 +/- 0.7 muU/mL in the II group (P < 0.0001, by ANOVA). No significant differences were observed in the normotensive control group. In conclusion, we extended previous data regarding the relationship of hypertension and IR by demonstrating a dependence of this relationship upon the ACE gene polymorphism.

Insertion/Deletion Polymorphism on ACE Gene is Associated with Endothelial Dysfunction in Young Patients with Hypertension

“…However, no association between I/D genotypes of ACE and plasma PAI-1 concentration was found by others [21,22]. The association between ACE gene polymorphism and insulin resistance (IR) in hypertensive subjects remains also controversial [23][24][25][26]. Perticone et al [24] referred that patients with the DD genotype never treated for hypertension had a higher fasting concentration of insulin and IR HOMA than the hypertensive patients with I allele of the ACE gene polymorphism.…”

Effects of Angiotensin II Type 1 Receptor Gene Polymorphisms on Insulin Resistance in a Japanese General Population: The Tanno-Sobetsu Study

“…Insulin resistance is closely linked to the metabolic syndrome (7), and the renin-angiotensin system (RAS) plays a central role in the regulation of insulin sensitivity (8)(9)(10), as well as in the regulation of blood pressure and sodium homeostasis (11). Many studies have examined the genetic involvement of homozygous deletion polymorphism (DD) in exon 16 of the angiotensin-converting enzyme gene (ACE) in insulin resistance, but their results have been controversial (12)(13)(14). The association between ACE insertion-deletion (I/D) polymorphism in intron 16 and cardiovascular phenotypes has also been studied, with the main result being that the D allele is a genetic risk for coronary artery disease or left ventricular hypertrophy (15,16).…”

Renin–angiotensin and endothelial nitric oxide synthase gene polymorphisms are not associated with the risk of incident type 2 diabetes mellitus: a prospective cohort study

“…While some studies found a significant association between the ACE I/D polymorphism and type 2 diabetes [12, 14, 25, 26], others did not [13]. Similarly, some studies found that individuals with the DD genotype had an increased insulin resistance [27], whereas others reported an increased insulin sensitivity in subjects with the DD genotype [28, 29]. Whilst several studies reporting a significant association were conducted in Asian populations [12, 25, 26], raising the possibility of differences across ethnicities, all of these studies were small.…”