Gender-Dependent Effect of ACE I/D and AGT M235T Polymorphisms on the Progression of Urinary Albumin Excretion in Taiwanese with Type 2 Diabetes

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.

Blood Pressure-Related Genes and the Progression of IgA Nephropathy

“…They proposed that TT genotype by itself was not enough to increase the risk of renal dysfunction and that the high blood pressure may have contributed to the renal progression. However, others reported that AGT genotype was not associated with the progression of diabetic nephropathy in either gender [30]. In present study, the development of hypertension during follow-up was similar between the different genotypes in either gender.…”

Genetic Predisposition to Diabetic Nephropathy: Evidence for a Role of ACE (I/D) Gene Polymorphism in Type 2 Diabetic Population from Kutch Region

“…Therefore, we suggest that the genetic variation at the ACE locus as D/D variant in intron 16, contribute to an increased risk of nephropathy in T2DM patients, but not extent of DN severity (as the allelic or genotypic distribution was comparable between the two DN groups) in studied population. Our findings were in conformity with other studies [26][27][28][29][30][31] but not all [32,55,56]. This difference may possibly be due to different races, methods of quantitation and patient selection; as proteinuria in adults is a multifactorial condition frequently linked with diabetes, the issue of whether proteinuria is due to diabetes or some other etiology remains debatable, but there was no uncertainty in our group of patients on the role of T2DM in diabetic nephropathy constitution as we excluded the patients who had proteinuria/renal disorders before their diabetes was diagnosed, thus we confined our study to diabetic kidney diseases.…”

“…Thus, the contribution of ACE gene polymorphism to the heritable part of risk for diabetic nephropathy seems important, and is supported by findings from published meta-analyses [28,62] along with other studies done among Indians [31,63], Japanese [29], French [64], Egyptian [65] and Taiwan [27] diabetic patients. However, our results do not coincide with studies done among Chinese [66], Tunisian [55], French [56], Turkish [34] and Iranian [67] diabetic cases.…”

“…This polymorphism was associated with circulating ACE levels [23][24][25] and owing to its central role in the regulation of blood pressure, sodium metabolism and renal hemodynamics [16,17], it is reasonable to hypothesize that genetic variation of ACE I/D contributes to the development of DN and numerous studies have addressed the role of this polymorphism in the complex etiology of DN, albeit with conflicting results i.e. several studies have demonstrated [26][27][28][29][30][31] or refuted [32][33][34] the role of ACE D variant as candidates for the development of DN. The discrepant finding among studies is attributed to genetic and environmental heterogeneity among different populations.…”

Apolipoprotein E Polymorphism and the Progression of Diabetic Nephropathy in Type 2 Diabetes

“…Albuminuria, elevated blood pressure (BP), and metabolic abnormalities explain only 30–50% of the variation in the progression of DN [3,4]. Familial clustering of diabetes and ethnic variation of DN suggest that hereditary factors also play an important role [5,6]. …”