Gender-dependent effect of ACE I/D and AGT M235T polymorphisms on the progression of urinary albumin excretion in Taiwanese with type 2 diabetes

Am J Nephrol. 2009;29(4):299-308. doi: 10.1159/000163592. Epub 2008 Oct 10.

Abstract

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.

Conclusion: Our follow-up study suggests that female diabetic carriers of the ACE D allele might be at an increased risk of DN progression.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Albuminuria / ethnology
  • Albuminuria / genetics*
  • Albuminuria / physiopathology
  • Angiotensinogen / genetics*
  • Diabetes Mellitus, Type 2 / ethnology
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diabetic Nephropathies / ethnology
  • Diabetic Nephropathies / genetics*
  • Diabetic Nephropathies / physiopathology
  • Disease Progression
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Peptidyl-Dipeptidase A / genetics*
  • Polymorphism, Genetic
  • Sex Characteristics*
  • Sex Distribution
  • Taiwan / epidemiology

Substances

  • Angiotensinogen
  • Peptidyl-Dipeptidase A