Relations between eNOS Glu298Asp polymorphism and progression of diabetic nephropathy.
BACKGROUND
Nitric oxide (NO) is related to the pathogenesis of renal hemodynamics in diabetes mellitus. Endothelial nitric oxide synthase (eNOS) gene polymorphism is considered the deterioration factor for progressive renal disease. It has been reported that an interaction of angiotensin II (Ang II) and NO is involved in the control of glomerular hemodynamics. This study aimed to elucidate the roles of eNOS and the angiotensin-converting enzyme (ACE) gene polymorphism for the progression of type 2 diabetic nephropathy (DN).


METHODS
Korean type 2 diabetic patients (n = 177) were studied. eNOS and ACE genotypes were determined by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) analysis. They were divided into three groups: group 1 consisted of patients with normoalbuminruia (n = 59), group 2 had microalbuminuria (n = 35) and group 3 had overt nephropathy (n = 83).


RESULTS
Group 3 had a higher frequency of eNOS(GT) than groups 1 and 2. Patients with eNOS(GT) genotype showed more rapid deterioration in renal function, higher incidence of overt nephropathy and lower renal survival than those with eNOS(GG) genotype. However, there was no significant association between the ACE genotypes and DN, and no interaction between eNOS and ACE gene polymorphism.


CONCLUSIONS
These results imply that eNOS(GT) genotype is associated with the progression of type 2 DN in Korean patients.
Shin Shin
Young
Y
Department of Internal Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Baek
Sang Hong
SH
Chang
Ki Yuk
KY
Park
Cheol Whee
CW
Yang
Chul Woo
CW
Jin
Dong Chan
DC
Kim
Yong Soo
YS
Chang
Yoon Sik
YS
Bang
Byung Kee
BK
D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000201:enzymology / Q000235:genetics*; D004151:Dipeptides / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012189:Retrospective Studies; D012307:Risk Factors
D004151:Dipeptides; C021030:gamma-glutamylaspartic acid; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D007703:Peptidyl-Dipeptidase A