Polymorphism of the aldosterone synthase gene is not associated with progression of diabetic nephropathy, but associated with hypertension in type 2 diabetic patients.
OBJECTIVE
Inhibition of aldosterone system is beneficial in diabetic nephropathy, and aldosterone synthesis is regulated at the gene-encoding aldosterone synthase (CYP11B2). Considering the role of aldosterone in diabetic nephropathy, genetic polymorphism of this gene may contribute to the development and progression of diabetic nephropathy. In this study, we investigated whether it is associated with diabetic nephropathy in type 2 diabetic patients.


METHODS
197 type 2 diabetic patients and 71 healthy controls were enrolled. The study subjects were divided into four groups: healthy controls with normoalbuminuria (n = 71), normoalbuminuric diabetic group (n = 71), microalbuminuric diabetic group (n = 51) and overt proteinuria group (n = 51). Polymorphism of aldosterone synthase gene was determined using standard PCR technique.


RESULTS
Higher frequency of TT genotype and T allele in steroidogenic factor-1 (SF-1) binding site and wild type (WT) in intronic conversion (IC) in CYP11B2 was observed in diabetic patients than controls. However, there was no significant difference in SF-1 and IC genotype among diabetic patients according to the state of diabetic nephropathy. Subgroup analysis based on SF-1 polymorphism demonstrated that TT genotype is associated with higher systolic and diastolic blood pressure and higher plasma aldosterone level. In addition, WT in IC genotype showed a significantly higher urinary albumin excretion rate. Plasma aldosterone level was significantly related with systolic blood pressure.


CONCLUSIONS
Our study suggests that aldosterone synthase gene polymorphism is not associated with progression of diabetic nephropathy, but it may contribute to the development of hypertension associated with increased aldosterone secretion in type 2 diabetic patients.
Ko
Gang Jee
GJ
Department of Internal Medicine, Korea University, Ansan City, Kyungki-Do, Seoul, Korea.
Kang
Young Sun
YS
Lee
Mi Hwa
MH
Song
Hye Kyoung
HK
Kim
Hyoung Kyu
HK
Cha
Dae Ryong
DR
D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000235:genetics; D003928:Diabetic Nephropathies / Q000209:etiology* / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000209:etiology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
D000450:Aldosterone; D019405:Cytochrome P-450 CYP11B2