Apolipoprotein E and ACE genetic polymorphism and nephropathy in type 2 diabetic patients / 대한내과학회지

BACKGROUND: The aim of this study was to investigate the association between apo E and ACE genetic polymorphism and diabetic nephropathy. METHODS: One hundred eighteen patients with type 2 diabetes who had a duration of diabetes longer than 8 years were divided into the three apo E groups (E2, E3, E4) and three ACE groups (II, ID, DD). Plasma levels of lipids were measured. The frequency of diabetic nephropathy and clinical and biochemical characteristics were compared among the Apo E and ACE genotype groups. RESULTS: The frequency of overt nephropathy was significantly greater in apo E2 patients with diabetes (46.7%) than apo E3 (16.7%) or apo E4 patients (10.5%). Logistical regression analysis showed that odds ratio of apo E2 and apo E4 genotypes for the presence of overt nephropathy were 4.779 (p<0.01) and 0.643 (p=0.583), respectively. Plasma TG levels were significantly greater in apo E2 patients. This study did not show an association between ACE gene polymorphism and diabetic nephropathy, and no interaction between Apo E and ACE gene polymorphism. CONCLUSION: Apo E2 is a prognostic risk factor for diabetic nephropathy in Korean type 2 diabetes. TG may have an important role of diabetic nephropathy. There were not synergistic effect between Apo E and ACE gene polymorphism in diabetic nephropathy.

Angiotensin Converting Enzyme Gene Insertion/Deletion Polymorphism and E-selectin S128R Polymorphism in Peripheral Atherosclerotic Occlusive Disease

PURPOSE: Studies concerning the relationship between gene polymorphisms and potentially implicated cardiovascular disease have produced conflicting findings, in part due to differences in ethnic background between populations. These led us to evaluate the impact of polymorphisms in the ACE and E-selectin genes on peripheral artery atherosclerosis in a Korean population. METHODS: We studied 92 male patients (median age: 65.9, range: 48~82) with severe peripheral atherosclerosis documented by angiography and ABI (ankle brachial index). The control group comprised 290 healthy persons (male 216, female 64, median age 61.3, range 20~90) without symptoms for peripheral vascular disease. The blood samples were stored at -20oC until DNA was ready to be extracted. The inorganic procedure for DNA extraction was based on the method described by Miller et al. The ACE and E-selectin polymorphisms were detected by polymerase chain reaction (PCR) amplification. RESULTS: The distribution of ACE genotypes of the patient group was as follows: II, 34 (37.0%); ID, 46 (50.0%); and DD, 12 (13.0%). It was not significantly different from that of the control subjects: II, 104 (37.1%); ID, 133 (47.6%); and DD, 43 (15.3%) (P=0.80). The allele frequencies of the patient group were as follows: I, 114 (62.0%); and D, 70 (38.0%). It was not significantly different from that of the control subjects: I, 341 (60.9%); and D, 219 (39.1%) (P= 0.80). The frequencies of E-selectin genotypes in the patient group were as follows: Ser/Ser 85 (93.4%); Ser/Arg, 6 (6.6); and Arg/Arg, 0 (0%). It was not significantly different from that of the control subjects: Ser/Ser, 262 (93.6%); Ser/Arg, 18 (6.4%); and Arg/Arg, 0 (0%) (P=0.95). In addition, the allele frequencies of the patient group were as follows: Ser, 176 (96.7%); and Arg, 6 (3.3%). It was not significantly different from that of the control subjects: Ser, 542 (96.8%); and Arg 18 (3.2%) (P=0.95). CONCLUSION: The I/D polymorphism of the ACE gene and E-selectin S128R polymorphism were not significantly different between the atherosclerotic patient group and the normal control group in Koreans.

Relationships between Angiotensin - Converting Enzyme Gene Polymorphism and Initiation and Progression of Renal Failure in Patients with Non-Insulin Dependent Diabetes Mellitus / 대한내과학회지

OBJECTIVE: Diabetic nephropathy is an important cause of end-stage renal disease and associated with morbidity and mortality of the patients with diabetes mellitus. It has been reported that the genetic susceptibility may be an important factor in the development of nephropathy in diabetic patients, but the genes responsible for the predisposition to diabetic nephropathy are not known. The genes of the renin-angiotensin systems are plausible candidate genes and the genetic polymorphism of angiotensin-converting enzyme(ACE) gene has been extensively studied for its possible role. Recently, the association of the ACE gene polymorphism with nephropathy as well as myocardial infartion was reported in diabetic patients. To elucidate the contribution of ACE gene polymorphism to the initiation and progression of diabetic nephropathy, we typed the alleles of the ACE gene in 139 patients with non-insulin dependent diabetes mellitus (NIDDM). METHODS: After the extraction of genomic DNA from peripheral blood leukocytes, PCRs were performed using the flanking and insertion specific primers, respectively. The PCR products were electrophoresed in 1.5% agarose gels, and DNA was visualized directly with ethidium bromide staining. RESULTS: Subjects were consisted of 139 patients with diabetes mellitus and male to female ratio was 63:76, mean age 55.8+/-12.0 years, mean duration of diabetes 9.5+/-7.8 years. ACE genotypes in whole population were 37.4% DD genotype, 51.1% ID genotype and 11.5% II genotype. The ACE genotype distributions, age, sex, blood pressure and body mass index were not different in diabetic subjects with or without nephropathy. No significant differences on the clinical parameters such as age, sex, blood pressure, body mass index, duration of diabetes, incidence of hypertension, cardiovascular complication, diabetic neuropathy and retinopathy, serum creatinine and 24hour albumin excretion were noted according to the ACE genotypes. Forty-six patients with NIDDM were followed over 3 years. The mean follow-up duration was 6.4+/-2.7 years, mean age was 54.4+/-10.2 years, and mean duration of diabetes was 14.7+/-6.1 years. ACE genotypes were 36.9% DD genotype, 52.2% ID genotype and 10.9% II genotype. The ACE genotype distributions were not different in the patients among DD, II or II genotypes. There were also no significant differences in terms of age, sex, duration of diabetes, blood pressure, body mass index, prevalence of hypertension, cardiovascular complication, diabetic neuropathy and diabetic retinopathy. But the rate of decline of creatinine clearance(deltacreatinine clearance, ml/min/year) was higher in DD genotype than ID or II genotypes(3.3+/-7.2 vs 2.8+/-6.2 vs 2.7+/-9.8), and the rate of change of 24-hour protein excretion(deltaurinary protein excretion, mg/24hours/year) was higher in DD genotype than ID or II genotypes(89.3+/-220.0 vs 74.1+/-156.8 vs 70.9+/-546.3). But they did not reach to statistical significance. CONCLUSION: We found that insertion/deletion polymorphism of ACE gene is not implicated in the initiation of diabetic nephropathy of Korean NIDDM patients, but also found the possibility that progression of diabetic nephropathy may be associated with it. We need large scaled prospective follow-up studies on the effects of ACE polymorphism in the progression of diabetic nephropathy.