Pharmacogenetics is the study of genetic influence on response to drugs. This is an area of increasing attention due to the possibilities of improving overall treatment effects in patients through individual strategies. Mogensen (1) addresses this subject and diabetic renal disease in relation to our study. In the study in question (2), we masked and prospectively investigated the renoprotective effects of angiotensin II receptor blockade (ARB) in hypertensive type 1 diabetic patients with diabetic nephropathy homozygous for the insertion (I) or deletion (D) allele of the ACE/ID polymorphism during 36 months of follow-up (2,3). We demonstrated that ARB by losartan confers similar beneficial renoprotective effects in patients with II and DD genotypes (2,3). Mogensen points out a contradiction between our present study (2) and our previous observational follow-up study of the influence of the ACE/ID polymorphism on the long-term efficacy of ACE inhibition in type 1 diabetic patients with diabetic nephropathy (4). The previous observational follow-up study demonstrated that DD patients have an accelerated rate of decline of the glomerular filtration rate during 7 years of ACE inhibition compared with patients with the I allele (4). We want to point out that the studies were carried out using two distinctly different types of drugs for blockade of the renin-angiotensin-aldosterone system, thus the results should not be expected to be identical. The present study using ARB was designed in an attempt to overcome the impeding interaction between ACE/ID genotypes and ACE inhibition by blocking the renin-angiotensin-aldosterone system at the receptor site (2,3). Therefore, demonstration of equal renoprotection in patients with DD or II ACE genotypes during ARB treatment is indeed distinct from our first study of ACE inhibition (4) and provides new and important information by identifying homozygous DD patients as a group that may receive specific benefits from ARB treatment. In addition, our present study is the first prospective pharmacogenetic study in diabetic nephropathy (2). The results indicate that there is a new light ahead in the treatment of diabetic nephropathy, but further pharmacogenetic studies should be carried out to identify patients who will benefit from treatment with particular drugs.
References
S.A. has received research support from Merck. H.-H.P. holds stock in Novo Nordisk, has received honoraria from Merck and Sanofi-synthelabo, and has received grants from Merck, Astra, and Sanofi-synthelabo.
