***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Diabetic nephropathy is one of the leading causes of end-stage renal disease . We examined whether ACE inhibitor treatment may have a nephroprotective effect in normotensive insulin-dependent diabetic patients without microalbuminuria and with normal glomerular filtration rate ( GFR ) , and whether any effect was associated with the ACE genotype . In a prospect i ve double-blind r and omized study , normotensive patients with type 1 diabetes mellitus with normal serum creatinine and no microalbuminuria were treated with either placebo or perindopril , an ACE inhibitor . Urine albumine/creatinine ratio ( ACR ) , mean blood pressure ( MBP ) and index of glomerular filtration rate ( GFR ) based on S-creatinine were determined . ACE genotype was determined by electrophoresis . ACR was higher in the placebo group than in the perindopril group after 4 months , and continued to increase during the study period . After 36 months of observation , ACR in the placebo group was 1.7+/-1.1 mg/mmol , and 0.6+/-0.2 mg/mmol in the ACE-inhibitor-treated group ( p<0.001 , Mann-Whitney test ) . During treatment , a significant increase in ACR in the placebo group ( p=0.007 ) , Wilcoxon matched paired test ) was observed . There were no differences between the groups regarding MBP or GFR . The nephroprotective effects of ACE inhibitor treatment was not associated with the ACE genotype ( II , ID , DD ) BACKGROUND In a previous study , men with a history of myocardial infa rct ion were found to have an increased prevalence of homozygosity for the deletional allele ( D ) of the angiotensin-converting-enzyme ( ACE ) gene . The D allele is associated with higher levels of ACE , which may predispose a person to ischemic heart disease . We investigated the association between the ACE genotype and the incidence of myocardial infa rct ion , as well as other manifestations of ischemic heart disease , in a large , prospect i ve cohort of U.S. male physicians . METHODS In the Physicians ' Health Study , ischemic heart disease as defined by angina , coronary revascularization , or myocardial infa rct ion developed in 1250 men by 1992 . They were matched with 2340 controls according to age and smoking history . Zygosity for the deletion-insertion ( D-I ) polymorphism of the ACE gene was determined by an assay based on the polymerase chain reaction . Data were analyzed for both matched pairs and unmatched sample s , with adjustment for the effects of known or suspected risk factors by conditional and nonconditional logistic regression , respectively . RESULTS The ACE genotype was not associated with the occurrence of either ischemic heart disease or myocardial infa rct ion . The adjusted relative risk associated with the D allele was 1.07 ( 95 percent confidence interval , 0.96 to 1.19 ; P = 0.24 ) for ischemic heart disease and 1.05 ( 95 percent confidence interval , 0.89 to 1.25 ; P = 0.56 ) for myocardial infa rct ion , if an additive mode of inheritance is assumed . Additional analyses assuming dominant and recessive effects of the D allele also failed to show any association , as did the examination of low-risk subgroups . CONCLUSIONS In a large , prospect ively followed population of U.S. male physicians , the presence of the D allele of the ACE gene conferred no appreciable increase in the risk of ischemic heart disease or myocardial infa rct ion The D/I ( deletion , D , insertion , I ) polymorphism of the angiotensin‐converting enzyme ( ACE ) gene has been extensively studied for its association with a number of cardiovascular and other disease states . However , its potential association with differential clinical efficacy of ACE inhibitors ( ACE‐I ) administered to patients who had suffered a myocardial infa rct ion ( MI ) , i.e. the prevention of left ventricular ( LV ) remodeling , has so far not been specifically studied . The aim of the study was to investigate whether the D/I polymorphism of the ACE gene is associated with the incidence of post‐MI LV remodeling in patients drawn from the ‘ Healing and Early Afterload Reducing Therapy ’ ( HEART ) Study . The ACE D/I polymorphism was characterized by the polymerase chain reaction ( PCR ) in 265 subjects from the ‘ Healing and Early Afterload Reducing Therapy ’ Study , a double‐blind , placebo‐controlled trial with the objective of determining whether early or delayed administration of the ACE‐I , ramipril , in patients with acute anterior wall MI would be optimal in reducing LV enlargement . Selected frequencies for the ACE D and I alleles were 0.59 and 0.41 ( placebo – high dose group ) , 0.56 and 0.44 ( low dose – low dose group ) , and , 0.60 and 0.40 ( high dose – high dose group ) , respectively . All observed genotype frequencies were in Hardy – Weinberg equilibrium . There was no evidence for an association between genotype and outcome regarding LV size or function , nor with the initial blood pressure response after ACE‐I administration ( adjusted for covariates ) . Our data provide no evidence for an association of the ACE D/I polymorphism with the risk of LV remodeling post‐MI in the presence of ACE‐I therapy , and therefore do not suggest that differential clinical efficacy of ACE‐inhibitors is related to this genetic marker BACKGROUND Cardiac complications are the main cause of death in renal transplantation ( RT ) , and left ventricular hypertrophy ( LVH ) may play an important role in these patients . The unfavorable genotype of the angiotensin-converting enzyme ( ACE ) gene has been associated with cardiovascular disease , including LVH . ACE inhibitors ( ACEIs ) reduce LVH , but little is known about the effects of ACEIs on LVH in RT patients with different insertion/deletion ( I/D ) genotypes of the ACE gene . METHODS We prospect ively studied 57 stable nondiabetic RT patients with hypertension and echocardiographic LVH as well as a functional graft for 69.5 + /- 5.6 months . Patients r and omly received either lisinopril 10 mg/day ( group A , N = 29 ; 5 were excluded due to reversible acute renal failure ) or placebo ( group B , N = 28 ) for 12 months . Echocardiography ( M-mode , 2-B , and color flow Doppler ) was performed at baseline and 6 and 12 months later by the same examiner without previous knowledge of the genetic typing . The ACE genotype ( I or D alleles ) was ascertained by polymerase chain reaction ( PCR ; group A , DD = 10 and ID/II = 14 ; group B , DD = 15 and ID/II = 13 ) . RESULTS All patients maintained a good renal function ( serum creatinine < 2.5 mg/dL ) during the follow-up and both groups received a similar proportion of antihypertensive drugs  ( beta-blockers 83 vs. 79 % ; Ca antagonists 66 vs. 68 % ; alpha1-adrenoreceptor antagonists 50 vs. 67 % ) during the study . As expected , mean arterial blood pressure and hemoglobin levels showed a higher percentage reduction in group A versus group B ( -4 + /- 2.8 vs. 2.1 + /- 2.6 % , P = 0.07 , and -11.5 + /- 1.5 vs. -0.5 + /- 2.3 % , P < 0.01 , respectively ) . Group A patients showed a significantly higher decrement in LV mass index ( LVMI ) than group B at the end of follow-up , after adjusting for age , baseline LVMI , time after grafting and changes in systolic blood pressure , renal function , and hemoglobin levels ( group A , -9.5 + /- 3.5 % vs. group B , 3 + /- 3.2 % , P < 0.05 ) . As a result , 46 % of group A and only 7 % of group B patients showed a reduction of LVMI > /=15 % ( P < 0.01 ) . The beneficial effect of lisinopril on LVMI reduction was more evident in DD patients ( placebo DD , 8.4 + /- 4.1 % vs. lisinopril DD , -7.2 + /- 5.3 , P < 0.05 ) , and a trend was observed in patients with other genotypes ( placebo ID/II , 2.8 + /- 5.4 % vs. lisinopril ID/II , -11.4 + /- 5 % , P = 0.33 ) . CONCLUSIONS Lisinopril decreases LVM in renal transplant patients with hypertension and LVH , and the ACE gene polymorphism may predict the beneficial effect of this therapy . This finding may be important in targeting prophylactic interventions in this population 
    Output:
    
The results may provide evidence for the usefulness of pharmacogenetic testing for individualised ACE inhibitor therapy