Association of Angiotensin Converting Enzyme Insertion-Deletion Polymorphism with Hypertension in Emiratis with Type 2 Diabetes Mellitus and Its Interaction with Obesity Status

Abstract

The association of Angiotensin Converting Enzyme (ACE) insertion-deletion (I/D) polymorphism with Type 2 Diabetes Mellitus (T2DM) and hypertension has been extensively studied throughout various ethnic populations but largely with inconsistent findings. We investigated these associations in Emirati population and their interaction with obesity status. Saliva samples were collected from a total of 564 Emiratis (277 T2DM and 297 healthy). DNA was extracted and the samples were genotyped for ACE I/D polymorphism by a PCR based method followed by gel electrophoresis. Upon evaluation of the ACE I/D polymorphism amongst all T2DM, hypertensive patients, and respective controls regardless of obesity status, ACE DD genotype was not found to be associated with either T2DM [odds ratio (OR) = 1.34, p = 0.086] or hypertension [odd ratio (OR) = 1.02, p = 0.93]. When the genetic variants amongst the nonobese and obese population were analyzed separately, the risk genotype ACE DD conferred significantly increased risk of hypertension in nonobese population [odds ratio (OR) = 1.80, p = 0.02] but was found to be protective against the hypertension in the obese group ((OR) = 0.54, p = 0.01). However, there was no effect of obesity status on the association of ACE genotypes with T2DM. The risk of hypertension associated with ACE DD is modulated by obesity status and hence future genetic association studies should take obesity into account for the interpretation of data. We also confirmed that ACE I/D polymorphism is not associated with T2DM risk in Emirati population.

Insertion / Deletion Polymorphism of Angiotensin Converting Enzyme Gene Does Not Contribute to Chronic Kidney Disease in Palestine

“…ACE genotype distribution differs from one population to another or even from one year to another in the same population. In Palestine, the D/D genotype was the most frequent genotype as demonstrated by the present study and this result is also similar to other studies [8,12], as it was shown to be the most frequent genotype in Iraq [13], while the I/D genotype was the most frequent genotype in Turkey [14] and the UAE [6]. Some countries like Egypt [15,16] have an inconstant frequency for the genotypes, and this may be related to the sample size, the population of the study or the techniques used in the determination of ACE gene polymorphism.…”

“…In terms of the association with HTN, it was not deemed to be statistically significant, and this result concurs with [8] and [14] but disagrees with Alsafar et al (2015) [6]. D/D genotype…”

“…Some countries like Egypt [15,16] have an inconstant frequency for the genotypes, and this may be related to the sample size, the population of the study or the techniques used in the determination of ACE gene polymorphism. However, other countries the distribution of the genotypes is constant, such as Palestine [12] and Iraq [13], also in this study ACE alleles frequency compared to different studies, where D allele was more frequent in this study and other studies [6,[12][13][14], whereas the I allele had the highest frequency in another study [16].…”

“…The Angiotensin Converting Enzyme (ACE) gene is one of the most studied genes that produce a protein that acts on Angiotensin I (AngI) to produce Angiotensin II (AngII), which is a potent vasoconstrictor in RAAS that regulates blood pressure and extracellular volume [6].…”

“…There are highly inconsistent findings within all the major ethnic groups when the association of I/D polymorphism of ACE gene is studied with cardiovascular and renal complications and the risk for Type 2 Diabetes Mellitus (T2DM), where some studies have explained that the D allele is most frequent in T2DM and the associated complications in Tunisia [10] while others have found no association between ACE alleles frequencies with T2DM or cardiovascular disease (CVD) and renal disease in Malaysia and Indonesians [11]. The differences in the findings are largely due to the multifactorial or polygenic nature of these disorders, as evidenced by the variations of disease outcomes modulated by the between the gene to gene or gene to environment interactions [6].…”