Albuminuria and the renin-angiotensin system gene polymorphisms in type-2-diabetic and in normoglycemic hypertensive Chinese.
BACKGROUND
Albuminuria predicts nephropathy-related mortality in Caucasian and Chinese populations. The involvement of renin-angiotensin system (RAS) gene polymorphisms in the pathogenesis of nephropathy has been described predominantly in Caucasian populations. We have previously suggested that the angiotensinogen 235T variant may be associated with nephropathy in diabetic Chinese.


METHODS
To validate these findings and extend them to include non-diabetic nephropathy, we examined the association of albuminuria and gene polymorphisms of the angiotensinogen M235T, angiotensin-converting enzyme insertion/deletion and angiotensin II type I receptor A1166C polymorphisms in 614 Chinese subjects (66% type 2 diabetic, 16% normoglycemic hypertensives and 18% controls).


RESULTS
Obesity and higher blood pressure were associated with albuminuria in both diabetes and normoglycemic hypertension. In the diabetic group, albuminuria was also associated with increased insulin resistance and glycemic indices, duration of diabetes and adverse lipid profiles. Only the ACE gene polymorphism showed evidence of association with albuminuria, with the D allele being less frequent in the normoglycemic hypertensive patients with albuminuria (25.0%) than the controls (41.4%) or normoalbuminuric group (39.6%) and in those hypertensives at increased risk (albumin-to-creatinine ratio > 5.6 mg/mmol) of end-stage renal disease than those at lower risk (all p < 0.05), but not in the diabetic group. The D allele was also less prevalent in the total (31.9%) and normoalbuminuric (32.2%) diabetic groups than in the controls (p < 0.05).


CONCLUSIONS
In this cohort of Chinese subjects, the ACE gene polymorphism D allele was less frequent in normoglycemic hypertensive patients with albuminuria and in type 2 diabetes.
Thomas
G N
GN
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, SAR. thomas1997@cuhk.edu.hk
Critchley
J A
JA
Tomlinson
B
B
Lee
Z S
ZS
Young
R P
RP
Cockran
C S
CS
Chan
J C
JC
D000328:Adult; D000419:Albuminuria / Q000235:genetics; D000808:Angiotensinogen / Q000235:genetics; D001786:Blood Glucose / Q000032:analysis*; D002681:China; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000652:urine; D005260:Female; D005787:Gene Frequency; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000235:genetics* / Q000652:urine; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D011945:Receptors, Angiotensin / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics*
D001786:Blood Glucose; D011945:Receptors, Angiotensin; D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A