Angiotensin-converting enzyme gene polymorphism and microvascular complications in Turkish type 2 diabetic patients

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Abstract

The aim of this study was to investigate whether an association exists between the angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism and microvascular complications of type 2 diabetes mellitus in Turkish patients. A total of 239 type 2 diabetic patients and 138 sex and age matched control subjects were included into the study. The I/D polymorphism was determined by polymerase chain reaction (PCR). Nephropathy status was determined according to urinary albumin/creatinine ratio (μg/mg) (<30 normoalbuminuria, 30–300 microalbuminuria, >300 macroalbuminuria) and retinopathy was evaluated by fundoscopic examination and by flourescein fundus angiography. The distribution of ACE I/D polymorphism and allele frequencies in diabetic patients were not significantly different from controls, DD genotype 32.2 versus 37.2%; ID genotype 50.6 versus 47.1%; and II 17.2 versus 15.2%; D allele 57.5 versus 61.2%; I allele 42.5 versus 38.8%. Genotype distribution between normo-, micro- and macroalbuminuric patients did not differ significantly (DD:ID:II (%), normoalbuminuria, 35:46:19; microalbuminuria, 28:55:17; macroalbuminuria, 31:55:14). There was also no difference in genotype distribution between patients with and without retinopathy (DD:ID:II (%), retinopathy positive, 32:51:17; retinopathy negative, 33:49:18). In conclusion, the ACE I/D polymorphism does not seem to be associated with diabetic nephropathy and retinopathy in Turkish type 2 diabetic patients.

Introduction

Nephropathy and retinopathy are major microvascular complications of both type 1 and 2 diabetes mellitus and the most common causes of end stage renal disease and blindness, respectively. In addition to many risk factors such poor glycemic control [1] and hypertension [2], recent studies have shown that genetic factors may play a role in the development of diabetic microvascular complications, especially diabetic nephropathy. One of the candidate genes that may be associated with diabetic nephropathy in type 2 diabetes mellitus is the insertion/deletion (I/D) polymorphism in intron 16 of the angiotensin converting enzyme (ACE) gene. Plasma ACE levels are affected mainly by this polymorphism and subjects that are homozygous for the deletion (DD), heterozygous (I/D) and those that are homozygous for the insertion (I/I) have the highest, intermediate and lowest ACE plasma levels, respectively [3]. It has been known that ACE contributes to the regulation of systemic and renal hemodynamics by converting angiotensin I to angiotensin II [4], a potent vasoconstrictor that increases intraglomerular pressure and glomerular filtration [5]. Therefore, it has been suggested that an elevation of ACE plasma concentration may be associated with the microvascular complications of diabetes. This suggestion is supported by the fact that ACE inhibitors have a beneficial effect on the initiation and progression of diabetic nephropathy [6], [7], [8], [9]. However, controversial observations were reported in regard to the possible relationship of ACE I/D polymorphism and diabetic nephropathy and retinopathy in different ethnicities.

Therefore, the aim of the present study was to investigate whether an association exists between the ACE I/D polymorphism and microvascular complications of type 2 diabetes mellitus in Turkish patients.

Section snippets

Study population

A cross-sectional/case-control study was conducted in the Department of Internal Medicine, Hospital of Sahinbey, Gaziantep University, Turkey. Two hundred and thirty-nine (151 female, 88 male; mean age 53.2±8.9; aged between 31 and 70 years; mean duration of diabetes 8.4±6.6 years) type 2 diabetic patients were included into the study. No patient was on haemodialysis. Age and sex matched 138 (87 female, 51 male; mean age 51.5±9.3; aged between 29 and 68) control subjects without diabetes were

Clinical and laboratory characteristics in the patient group

Table 1 represents certain clinical and laboratory data in the patient group according to the ACE genotype. When laboratory values were compared among different genotypes of type 2 diabetic patients, no significant difference was detected with regard to age, sex, diabetes duration, BMI, systolic and diastolic blood pressure, HbA1c, serum triglyceride, total cholesterol, LDL-cholesterol or HDL-cholesterol (Table 1). However, patients with macroalbuminuria had longer diabetes duration, higher

Discussion

The development of diabetic nephropathy shows marked interethnic and inter-individual variation. Epidemiological studies showed a higher prevalence of diabetic nephropathy in non-whites than in whites [11], [12], [13]. In some diabetic patients, nephropathy develops in short-term disease duration, despite similar glycemic control and blood pressure among patients. On the other hand, in nearly all patients with type 1 diabetes mellitus, retinopathy develops with a long disease duration [14], [15]

Acknowledgements

This study was supported by a grant of the Research Foundation of University of Gaziantep, Turkey (Grant no. TF99-01).

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