Gender-dependent effect of ACE I/D and AGT M235T polymorphisms on the progression of urinary albumin excretion in Taiwanese with type 2 diabetes.
BACKGROUND
We investigated the gender differences in the effect of ACE I/D and AGT M235T polymorphisms on the prognosis of diabetic nephropathy (DN).


METHODS
A total of 525 type 2 diabetics were enrolled to participate in this prospective observational study. ACE and AGT gene polymorphisms were analyzed by polymerase chain reaction. The progression of DN was defined as a shift to a higher stage of DN or a doubling of the baseline serum creatinine level by the end of the study.


RESULTS
The baseline biophysical parameters show no gender differences in progression and non-progression of DN. The women who were ACE D allele carriers were found to be at an increased risk of DN progression compared to those with II genotypes (p = 0.024, OR 2.176). No such difference was seen in male patients (p = 0.619, OR 0.833). After adjusting for confounding factors (age, SBP, DBP, BMI, HbA1c, total cholesterol, TG, HDL-C, LDL-C, ACEI, and ARB) in our multiple regression analysis, these women were still found to be at increased risk of progressing to more severe DN (p = 0.008, OR 3.082) but not the men (p = 0.183, OR 0.586). Neither the AGT TT genotype nor the T allele were associated with the progression of DN in either sex after adjusting for confounding factors.


CONCLUSIONS
Our follow-up study suggests that female diabetic carriers of the ACE D allele might be at an increased risk of DN progression.
Tien
Kai-Jen
KJ
Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Hsiao
Jeng-Yueh
JY
Hsu
Shih-Chieh
SC
Liang
Hui-Ting
HT
Lin
Shiu-Ru
SR
Chen
Hung-Chun
HC
Hsieh
Ming-Chia
MC
D000368:Aged; D000419:Albuminuria / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D000808:Angiotensinogen / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D012727:Sex Characteristics; D017678:Sex Distribution; D013624:Taiwan / Q000453:epidemiology
D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A