Ace Insertion/deletion Gene Polymorphism Determines Efficacy of Telmisartan: an Arb in Type 2 Diabetic Nephropathy

Activation of the renin-angiotensin-aldosterone system plays a critical role in the initiation and progression of diabetic nephropathy. The blockade of the renin-angiotensin system is the major target of efforts to prevent the progression of chronic kidney disease (CKD). Favorable effects of angiotensin receptor blockers (ARBs) in diabetic nephropathy are well known. However, genetic determinants of the response to ARBs remain unclear, therefore, ACE gene insertion/ deletion (I/D) polymorphism may reveal the genetic basis for differential response to ARB’s, in diabetic nephropathy. We evaluated the correlation between Insertion/ Deletion polymorphism of ACE gene and the response to Telmisartan-an ARB, on various clinical and biochemical parameters in Type 2 diabetic nephropathy. In his prospective, cross-sectional, open label, observational study, 30 cases of T2DM were evaluated, regarding diabetic nephropathy, renal insufficiency and hypertension. All patients underwent detailed clinical and biochemical evaluation at baseline and post-Telmisartan 20mg/day at 12 week. Genomic DNA fragment on intron 16 of the ACE gene was amplified by polymerase chain reaction (PCR), followed by sequencing. Differences among mean values have been evaluated by analysis of variance ANOVA or ANCOVA, as appropriate. A p value (two sided) of < 0.05 was considered to be significant. All calculations were performed using SPSS-11.0 (Chicago, IL, USA). The mean age of this study group was 45.21 ± 2.34 yrs. The mean age of thirteen females was 44.36 ± 4.21yrs, while that of seventeen males was 46.08 ± 3.74 years. PCR amplification of ACE gene fragment followed by sequence analysis which revealed I/I, (n =8) I/D (n = 18 and D/D (n = 4), types of polymorphism. All the patients were comparatively evaluated. Age wise, all three groups were matched (p=0.012), micro and macro-vascular complications were more prevalent in DD type, where retinopathy and CAD was present in 100% and 75% cases, respectively. In patients having genotype II (n = 8), majority (75%) of patients took longer time >5 yr, to develop overt albumiuria, having lesser degree of hypertension, renal dysfunction, and dyslipidemia than ID and DD genotypes (p<0.005). The D/D carriers and I/D carriers did not benefit significantly from telmisartan therapy while I/ I carriers showed significant treatment responses regarding urinary albumin excretion (UAE), SBP, DBP, TG, S.Cr. and LDL-C were significantly higher (p<0.005), in patients of DD type than II and ID groups. This finding suggests that ACE insertion/deletion polymorphism is associated with Diabetic nephropathy in Asian Indians. In the present study, it was found that patients with deletion DD polymorphism have significant renal dysfunction, albuminuria and progressive diabetic nephropathy. The D/D and I/D genotypes did not benefit significantly from telmisartan therapy while I/I genotype showed significant treatment responses.