The ACE DD genotype was associated with increased risk of type 2 diabetes (OR 4.37), hypertension (OR 9.0), and chronic kidney disease (OR 5.73) compared to the II genotype.
Case-Control (n=105)
Is the ACE gene I/D polymorphism associated with an increased risk of type 2 diabetes mellitus, hypertension, and chronic kidney disease in a South Indian population?
The DD genotype and D allele of the ACE I/D polymorphism are associated with an increased risk of T2DM, hypertension, and CKD in a South Indian population.
Effect estimate: OR 4.37 (T2DM), OR 9.0 (HT), OR 5.73 (CKD) (95% CI 1.31-14.504 (T2DM), 2.23-36.17 (HT), 1.906-17.282 (CKD))
p-value: p=0.05
Background: The renin–angiotensin–aldosterone system (RAAS) is important in regulating blood pressure and electrolyte balance. The main effector hormone of the RAAS is angiotensin II, which is generated from angiotensin I in the circulation and in the tissues, mostly as a result of the action of angiotensin-converting enzyme (ACE). The ACE gene has received substantial attention in recent years as a candidate gene for a variety of diseases. Objective: This study was conducted to determine the association of insertion/deletion (I/D) polymorphism of ACE gene in type 2 diabetes mellitus (T2DM), hypertension (HT), and chronic kidney disease (CKD) subjects among South Indian regional population. Methods: A total of 105 subjects participated in this study including 30 T2DM (Group 1), 30 HT (Group 2), 35 CKD (Group 3) patients and 10 controls (Group 4). Blood samples were collected and biochemical investigations were done. Polymerase chain reaction amplification was performed to genotype the DNA. The distribution and allelic frequency of I/D (rs1799752) polymorphism at the 287-base pair Alu repeat sequence in the intron 16 of ACE gene were analyzed using specific primers. Results: The ACE genotypes were distributed as II, 17%; DD, 47%; and ID, 37% in the T2DM group; II, 10%; DD, 50%; and ID, 40% in the HT group; II, 17%; DD, 54%; and ID, 29% in the CKD group; and II, 50%; DD, 20%, and ID, 30% in the control group. The frequency of DD genotype was significantly higher in HT ( P = 0.05) and CKD patients ( P = 0.05) compared to controls. In codominant model analysis, DD genotype versus II genotype was associated with increased risk of T2DM (odds ratio OR = 4.37; 95% confidence interval CI = 1.31–14.504), HT (OR = 9.0; 95% CI = 2.23–36.17), and/or CKD (OR = 5.73; 95% CI = 1.906–17.282), respectively. The D allele was more frequent in T2DM (65%), HT (70%), and CKD patients (69%) compared to controls (35%) ( P = 0.018, P = 0.005, and P = 0.006, respectively). The D allele was associated with increased risk of T2DM (OR = 3.44; 95% CI = 1.19–9.96), HT (OR = 4.33; 95% CI = 1.48–12.65), and CKD (OR = 4.05; 95% CI = 1.42–11.55). Conclusion: The DD genotype and the D allele of the ACE I/D gene polymorphism can be a risk factor for T2DM, HT, and CKD in South Indian regional population. This result suggests that T2DM and HT patients should be offered analysis to identify defects in ACE I/D polymorphism, which might help to determine the course of CKD disease and aid to choose appropriate antihypertensive therapy with ACE inhibitor/angiotensin receptor blockers.
Ramanathan et al. (Fri,) conducted a case-control in Type 2 diabetes mellitus, hypertension, and chronic kidney disease (n=105). ACE gene I/D polymorphism (rs1799752) vs. Healthy controls / II genotype was evaluated on Risk of T2DM, HT, and CKD associated with DD genotype versus II genotype (OR 4.37 (T2DM), OR 9.0 (HT), OR 5.73 (CKD), 95% CI 1.31-14.504 (T2DM), 2.23-36.17 (HT), 1.906-17.282 (CKD), p=0.05). The ACE DD genotype was associated with increased risk of type 2 diabetes (OR 4.37), hypertension (OR 9.0), and chronic kidney disease (OR 5.73) compared to the II genotype.