ACE gene polymorphism and progression of diabetic nephropathy in Korean type 2 diabetic patients: effect of ACE gene DD on the progression of diabetic nephropathy.
BACKGROUND
Pathophysiological causes of the development and progression of diabetic nephropathy are not well known, but the angiotensin-converting enzyme (ACE) gene polymorphism has been proposed to be involved in its development and progression.


METHODS
The impact of insertion/deletion (I/D) genotypes on the progression of diabetic nephropathy in 239 Korean patients with type 2 diabetes (99 patients with stable renal function, group 1; 140 patients with declining renal function, group 2) was investigated by retrospective review of clinical data.


RESULTS
The frequency of the DD genotype was significantly greater in group 2 compared with group 1 (30.7% versus 9.1%; P < 0.05). There were no significant differences in age, blood pressure, hemoglobin A(1c) levels, or lipid profiles among ACE genotype groups. However, the prevalence of retinopathy was significantly greater in patients with the DD genotype (DD, ID, and II, 90.4%, 71.2%, and 70.6%, respectively; P < 0.05). Patients with the DD genotype reached the end point (serum creatinine > 2.0 mg/dL [176.8 micromol/L]) faster than those with the other genotypes (DD, 11.38 +/- 4.08 years; ID, 13.85 +/- 4.04 years; II, 14.04 +/- 4.06 years, respectively; P < 0.05) and took significantly less time to reach dialysis therapy (DD, 13.10 +/- 4.45 years; ID, 16.21 +/- 4.74 years; II, 15.13 +/- 4.09 years, respectively; P < 0.05). In multiple logistic regression analysis, systolic blood pressure and DD genotype showed significant correlations with the progression of diabetic nephropathy. In patients with the DD genotype, the odds ratio was 3.881 (95% confidence interval, 1.564 approximately 9.628; P = 0.003) compared with those with the II genotype.


CONCLUSIONS
It is suggested that the ACE gene DD genotype might be a significant risk factor for the progression of diabetic nephropathy.
Department of Internal Medicine, College of Medicine and Brain Korea 21 Project for Medical Science, Yonsei University, Seoul, South Korea. hask1951@yumc.yonsei.ac.kr
Sung-Kyu
SK
Ha
Hyeong Cheon
HC
Park
Hong Su
HS
Park
Byung Seung
BS
Kang
Tae Hee
TH
Lee
Hak Jin
HJ
Hwang
Seung Jung
SJ
Kim
Do Hun
DH
Kim
Shin Wook
SW
Kang
Kyu Hun
KH
Choi
Ho Yung
HY
Lee
Dae Suk
DS
Han
D003404:Creatinine / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000209:etiology / Q000235:genetics* / Q000628:therapy; D018450:Disease Progression; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D007723:Korea; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D006435:Renal Dialysis
D003404:Creatinine; D007703:Peptidyl-Dipeptidase A