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Genotypes and viremia of hepatitis B and D viruses are associated with outcomes of chronic hepatitis D patients.

BACKGROUND & AIMS: Genotypes and viremia of hepatitis D virus (HDV) and hepatitis B virus (HBV) may be associated with outcomes. This study evaluated the impact of viral genotypes and viremia on outcomes of dual HBV and HDV infection. METHODS: Viremia and viral genotypes were analyzed in 194 consecutive chronic hepatitis B patients with HDV superinfection and correlated with outcomes. RESULTS: The numbers of HBV genotype A, B, C, and nonclassified were 4, 57, 23, and 110, respectively. There were 51 genotype I HDV, 74 genotype II HDV, 8 genotype IV HDV, and 61 nonclassified HDV genotype. In a median follow-up of 135 months, 24 progressed to cirrhosis and 41 developed hepatocellular carcinoma. Patients infected with genotype I HDV had a lower remission rate (15.2% vs 40.2%; P = .007) and more adverse outcomes (cirrhosis, hepatocellular carcinoma, or mortality) (52.2% vs 25.0%; P= .005) than those with genotype II HDV. Patients infected with genotype C HBV had a lower remission rate (0 vs 32.1%; P = .005) and more adverse outcomes (70.0% vs 33.9%; P = .005) than those with genotype B HBV. The presence of HBV or HDV viremia was associated with lower remission rates compared with those negative for both (26.4% and 24.3% vs 69.2%; P < .001). In multivariate analysis, age, genotype C HBV, and genotype I HDV were independent factors associated with adverse outcomes. CONCLUSIONS: In chronic HBV and HDV dual infections, older age, genotype I HDV, and genotype C HBV correlated with adverse outcomes.

Adult↗

Genotyping of hepatitis D virus by restriction-fragment length polymorphism and relation to outcome of hepatitis D.

The outcome of hepatitis D virus (HDV) superinfection varies among patients and in different geographical areas. To find out whether HDV genotype affects outcome, we used a simple genotyping method based on restriction-fragment length polymorphism with enzymes XhoI and SacII for cleavage of PCR products of the HDV genome. Of samples from 88 patients studied, the genotypes of 61 were confirmed by two methods--analysis with both enzymes or by combined restriction-enzyme and direct sequencing analyses--with consistent results. No genotype III HDV was detected among these patients. The majority of patients with acute HDV infection (35/41 [85%]) had genotype II HDV. Among the 41 patients with acute infection, four of six with genotype I had fulminant disease compared with two of 35 with genotype II. Among patients in chronic stage, cirrhosis or hepatocellular carcinoma were found in 12 of 18 with genotype I HDV and eight of 29 with genotype II. Thus genotype II was the predominant HDV genotype in this study in Taiwan. Genotype II HDV was less frequently associated with fulminant hepatitis at the acute stage or with an unfavourable long-term clinical outcome at the chronic stage than was genotype I.

Acute Disease↗

[Polymorphism of ACE gene and its relationship with serum ACE activity in the Hans in Chengdu region].

This study was aimed at the angiotensin converting enzyme (ACE) gene insertion/deletion(I/D) polymorphism distribution in Chinese and its relationship with serum ACE activity(SACE). SACE activity and ACE gene polymorphism in 90 healthy persons in Chengdu region were investigated using a spectrophotometric assay and the PCR technique, respectively. The results showed that, in the Hans, DD genotype of ACE gene was 18%, DI genotype 44%, and II genotype 38%. Allele frequencies were 0.40 for the D allele and 0.60 for the I allele. There were significant relationships between ACE I/D polymorphism and SACE activity. The results suggest that ACE genotype distribution be different between races, that II genotype and I allele be more frequent in Chinese, and that SACE activity be under the influence of a genetic polymorphism of ACE in Chinese.

Adult↗

[Correlative study between angiotensin-converting enzyme gene polymorphism and hepatorenal syndrome].

OBJECTIVE: To investigate the relationship between insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE) gene and uncompensated cirrhosis of liver with hepatorenal syndrome (HRS). METHODS: ACE I/D polymorphism was detected by polymerase chain reaction amplification of DNA fragment in 56 patients of uncompensated liver cirrhosis with HRS, and 60 healthy individuals served as the controls. At the same time, alanine aminotransferase, aspartate transaminase, serum creatinine (SCr), blood urea nitrogen (BUN) and glomerular filtration rate (GFR) etc. were measured in all the subjects, and the difference between these variables among different genotypes was noted. RESULTS: There was no significant difference in genotypes and allele frequency between the HRS group and controls(all P>0.05). The I allele frequency was higher than the D allele in all the subjects (all P<0.01). But in the control group, there was no significant difference in the genotype frequency among three genomic groups, while the II genotype frequency was higher than the one of ID and DD (all P<0.05). SCr and BUN of the II genotype were higher in the HRS group than that of ID and DD(both P<0.05) and GFR of the II genotype was lower than the one of ID and DD in the HRS group(P<0.05). CONCLUSION: There is relationship between ACE gene polymorphism and the incidence of uncompensated liver cirrhosis with HRS. II genotype may be the genetic factor of vulnerability to HRS patients with uncompensated cirrhosis of liver. The degree of kidney failure in II genotype population is more serious than in ID and DD individuals with uncompensated liver cirrhosis complicated by HRS.

Adult↗

Carotid remodeling of hypertensive subjects and polymorphism of the angiotensin-converting enzyme gene.

BACKGROUND: This study was designed to investigate the relationships between changes in the structure and function of carotid arteries and angiotensin converting enzyme (ACE) gene polymorphism in Chinese hypertensive subjects. METHODS: Multiplex polymerase chain reaction amplification was used to evaluate the ACE gene insertion/deletion (I/D) polymorphism. High-resolution B-mode ultrasound examinations were performed to detect parameters of carotid artery remodeling. RESULTS: Intima-media thickness (IMT) was significantly different among the DD, ID and II genotypes of ACE (DD > ID > II, P < 0.05). Carotid internal diameter, distensibility and stiffness were similar among the DD, ID and II genotypes of ACE (P > 0.05) in hypertensive subjects. The frequency of the DD gene and D allele of ACE were higher in patients with thickening carotid than in patients with normal carotid (70.4% vs 24.1%, and 79.5% vs 40.5%, respectively, P < 0.001). In multiple stepwise regression analysis, independent risk factors for increased carotid IMT in hypertensive subjects were ACE genotypes (P < 0.001), age (P < 0.001) and carotid internal diameter (P = 0.032). Moreover, triglycerides and total cholesterol were higher in patients with the DD genotype than in those with the II genotype (P < 0.05). CONCLUSIONS: The I/D polymorphism of the ACE gene was related to IMT, but not to internal diameter, distensibility and stiffness of the carotid in Chinese hypertensive subjects. ACE gene polymorphism was a main risk factor for increased carotid IMT. These results may imply that there is a link between lipid metabolism and ACE genotype polymorphism in Chinese hypertensive subjects.

Asian People↗

The ACE gene polymorphism and cough threshold for capsaicin after cilazapril usage.

Persistent dry cough is an occasional but clinically important adverse reaction to angiotensin I-converting enzyme (ACE) inhibitors (ACEI). Its reported incidence is variable, and why cough occurs in only certain individuals has been unclear. An insertion/deletion (I/D) polymorphism of the ACE gene is associated with serum ACE activity. We have previously shown that susceptibility to cough induced by ACEI is associated with this polymorphism such that patients with genotype II are more susceptible to cough than patients with other genotypes. In order to confirm and extend our previous observation, we conducted a randomized, placebo-controlled, double-blind, cross-over study in 10 healthy volunteers with genotype II and 10 with genotype DD. The cough threshold was determined by the concentration of inhaled capsaicin causing two or more coughs. After the usage of an ACEI, cilazapril, for 4 weeks, changes in the cough threshold in subjects with genotype II [before: 6.6+/-3.7 nM (mean+/-SD); after: 5.0+/-4.6 nM] significantly differed from those in subjects with genotype DD (before: 9.0+/-9.4 nM; after: 9.3+/-9.1 nM). Skin responses to intradermal bradykinin, which is a substrate of ACE and tussigenic, were significantly increased in subjects with genotype II (before: 1.6+/-0.6 vs. after: 2.6+/-0.5 cm2, P<0.05) but not in subjects with genotype DD (before: 1.4+/-0.5 vs. after: 1.6+/-0.6 cm2, n.s.) after usage of cilazapril. By contrast, skin responses to intradermal substance P did not change in subjects with either genotype. These findings provide further evidence of a link between ACEI-induced cough and I/D polymorphism of the ACE gene and suggest that ACEIs induce cough by modulating the tissue level of bradykinin.

Adult↗

Association between angiotensin converting enzyme gene polymorphism and coronary artery disease in individuals of the South-Eastern Anatolian population.

OBJECTIVE: The deletion (D) allele of the angiotensin-converting enzyme (ACE) gene has been proposed as a genetic marker of the risk of coronary artery disease (CAD). In this study we aimed to determine the relevance of ACE gene polymorphism for coronary artery disease in the South-Eastern Anatolian population. METHODS: Angiotensin converting enzyme genotypes were determined in 133 CAD patients who underwent coronary angiography. Severity of CAD was subgrouped according to the number of stenotic vessels on coronary angiography. The control group was selected from 154 healthy volunteers. Angiotensin converting enzyme genotypes were determined by agarose gel sizing after polymerase chain reaction (PCR) amplification. RESULTS: Frequency of ACE DD genotype did not differ between patients with CAD and control subjects. However the ACE II genotype in CAD group was significantly less frequent than in control group (p=0.02). The relative risks were 0.9 (95% CI=0.56-1.43) for the DD genotypes, and 2.2 (95% CI=1.09 - 4.11) for the II genotype. In the 2-vessel CAD subgroups, the II genotypes were significantly different from control group. CONCLUSION: Our study did not confirm the possibility that the ACE DD genotypes may be associated with predisposition to CAD in this certain population but there is a relationship between the least frequencies of the II genotype and CAD. The II genotype seems to be an independent protective factor for CAD in the South-Eastern Anatolian population.

Adult↗

Relation between the angiotensin-converting enzyme insertion/deletion polymorphism and blood pressure in Japanese male subjects.

Inconsistent results have been reported regarding the association of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and hypertension. Recent studies of population-based samples of three different areas in Japan presented conflicting results regarding this association. We, thus, investigated the relation between the ACE I/D polymorphism and blood pressure (BP), or the frequency of hypertension, respectively, in 706 Japanese male subjects who participated in the health check-up programme of our hospital. The ACE I/D polymorphism was determined by the polymerase chain reaction technique. Of 706 subjects, 203 were found to have hypertension and the other 503 were found to be normotensive. In all subjects, the frequencies of the DD, ID, and II genotypes were 0.123, 0.432, and 0.445, respectively, and the allelic frequency of the D allele was 0.339. In the younger subjects aged <50 years (n=264), neither systolic nor diastolic BP differed significantly among the genotypes. Conversely, in the older subjects aged > or =50 years (n=442), the systolic BP was significantly higher by 5.9 mmHg in the subjects with the ID genotype than those with the II genotype (P<0.01), and the diastolic BP was significantly higher in the subjects with the DD and ID genotypes by 5.1 and 3.3 mmHg, respectively than those with the II genotype (P<0.05 for each), although age, BMI, percentage of smoking habits, drinking habits, or the use of antihypertensive drugs did not differ significantly among the genotypes. In addition, in the older subjects, the hypertensive subjects showed significantly higher frequencies of the DD and ID genotypes and the D allele than the normotensive subjects. These results demonstrated that there was no significant association of the ACE I/D polymorphism with BP or a prevalence of hypertension in younger Japanese men aged <50 years but there was in older Japanese men aged > or =50 years.

Adult↗

[The relationship between polymorphism of angiotensin converting enzyme gene and cough caused by angiotensin converting enzyme inhibitors].

OBJECTIVE: To investigate the relationship between the polymorphism of angiotensin converting enzyme (ACE) gene and ACE inhibitor (ACEI)-induced cough in Chinese elderly with essential hypertension. METHODS: ACE I/D polymorphism was performed on DNA samples from patients using the polymerase chain reaction (PCR) followed by agarose gel electrophoresis. Serum ACE levels were measured using a colorimetric assay. RESULTS: The frequencies of ACE II genotype were 40% in patients with cough and 20% in those without cough, respectively (P < 0.05). The frequencies of I allele were 60% in patients with cough and 41% in those without cough (P < 0.01); The serum ACE level was highest in the DD genotype, followed by the ID genotype and the II genotype. The ACE level in patients with cough was significantly lower than that in patients without cough (P < 0.001). The sensitivity and specificity were 81% and 78% respectively when the serum ACE levels were used to predict ACEI-induced cough. CONCLUSION: ACEI-induced cough was related to the serum ACE level and ACE gene polymorphism in Chinese elderly with essential hypertension.

Aged↗

Egyptian genotyping of Giardia lamblia.

Out of 105 patients infected with Giardia, 38 patients have Genotype I (36.19%), 13 have Genotype II (12.38%), 10 have Genotype III (9.52%), 16 have mixed Genotype infection (15.24%) and 28 with undetermined Giardia infection by PCR (26.67%). None of the control group gave positive results for Giardia in stool by PCR. So, the sensitivity of the test for detection and identification of Giardia Genotypes from the original stool samples was 73.33% and specificity was 100%. Out of 61 cases in the symptomatic group, the prevalence of Giardia Genotype I was 32.79%, Genotype II was 16.39%, Genotype III was 9.84%, mixed Genotype infection was 16.39% and undetermined Genotype was 24.59% as compared to 40.91%, 6.82%, 9.09%, 13.64% & 29.55% in the asymptomatic group respectively. There is statistically insignificant difference between both groups as regarding the prevalence of the different Giardia Genotypes. (P < or = 0.05). The use of PCR as a routine work for diagnosis of giardiasis is not accepted at least in the developing and under-developing countries due to its high cost, the high quality of technical staff and advanced laboratory equipments required for PCR performance. Its application is usually limited to research activities, the detection of water sources contamination and for the detection of a potential source of Giardia infection in epidemics.

Adolescent↗

[Polymorphism studies of angiotensin converting enzyme gene in chronic glomerulonephritis].

AIM: To investigate the relationship between polymorphism of angiotensin-converting enzyme (ACE) gene and predisposition to chronic glomerulonephritis (CGN) as well as antihypertensive and anti proteinuric response to ACE inhibitors (ACEI) treatment, therapy with angiotensin II receptor antagonists. MATERIALS AND METHODS: Genotype was determined in 57 CGN patients and 113 subjects free of chronic diseases. Effects of ACE gene polymorphism on antihypertensive and antiproteinuric efficiency of ACEI and cozaar were studied in 35 CGN patients on monotherapy. 24-h proteinuria, levels of creatinine, potassium in the serum, arterial pressure, glomerular filtration rate were measured in all the patients. RESULTS: No significant differences were found between incidence of ACE gene genotypes and alleles in patients with CGN and controls. Maximal antihypertensive response to therapy was observed after a month treatment in patients with genotypes II and ID. Lowering of arterial pressure in patients with genotype DD was observed on month 6-12 of continuous therapy. Proteinuria diminished on the treatment month 1-3 in patients with genotypes II and ID, in genotype DD proteinuria rose for the same period of time. Proteinuria dropped similarly in all the groups by month 6-12. CONCLUSION: Relations between ACE gene polymorphism and genetic predisposition to CGN were not found. Patients with genotype II were most sensitive to IACE and cosaar treatment. Lack of an early anti proteinuric response in homozygotes DD does not determine effectiveness of long-term IACE treatment and should not be a reason for the above drug discontinuation.

Adolescent↗

Hepatitis delta virus genotype IIb predominates in an endemic area, Okinawa, Japan.

Hepatitis delta virus (HDV) infection is relatively common in the Miyako Islands, Okinawa, Japan, where the infection has been reported to be associated with low pathogenicity. HDV RNA extracted from each of 6 patients with HDV-related chronic liver disease living in the islands was amplified by reverse transcription-polymerase chain reaction and examined genetically to determine the HDV genotype. All isolates from the 6 patients were classified as genotype II by the neighbor-joining method. However, these isolates had relatively low homology (75-81%) to the HDV genotype II isolate reported from Japan, and showed relatively high identity (83-95%) to the novel genotype II isolate (HDV genotype IIb) recently reported from Taiwan. Phylogenetic analysis showed that the 6 isolates form a novel group within HDV genotype II. Furthermore, there was notable variation in sequence among the 6 isolates compared with the relatively close clustering of HDV isolates within limited areas (e.g., United States, Archangelos, Turkey, Albania, Peru). HDV genotype II in the Miyako Islands is therefore unique, and HDV infection may have been introduced at a relatively early time in this area.

Adult↗

Angiotensin-converting enzyme insertion/deletion polymorphism and prognosis of IgA nephropathy.

BACKGROUND/AIM: Well-known factors for a poor prognosis in IgA nephropathy (IgAN) are hypertension, proteinuria, and renal insufficiency at the time of diagnosis. Also hypertriglyceridemia and hyperuricemia seem to play a role in the progression of IgAN. Angiotensin-converting enzyme (ACE) gene I/D polymorphism has been associated with cardiovascular diseases and with progression of IgAN. We, therefore, investigated the contribution of ACE gene I/D polymorphism in the prognosis of IgAN and its association with the other risk factors affecting the prognosis. METHODS: A total of 168 patients with IgAN were followed up for 6-17 (median 11) years from renal biopsy with respect to progression of renal disease defined as elevation of serum creatinine above 125 microM (1.4 mg/dl) in men or 105 microM (1.2 mg/dl) in women and over 20% from the baseline level. In addition to serum creatinine, the urinary protein excretion was evaluated at the time of renal biopsy and at the assessment visit at the end of the follow-up period. RESULTS: During the follow-up period, 26 (15%) patients showed progression of renal disease. Patients with ACE genotype II had a more favorable course than those with genotypes ID or DD. Although there were no significant differences among the ACE genotypes with respect to proteinuria > or =1 g/24 h at the time of renal biopsy, proteinuria > or =1 g/24 h was more frequent in patients with genotypes ID or DD than in those with genotype II at the end of the follow-up period. No associations were found between hypertension, serum lipids or serum urate, and ACE genotypes. CONCLUSIONS: Our results show that patients with ACE genotype II have a more favorable prognosis than those with genotypes ID/DD. Secondly, proteinuria (> or =1 g/24 h) found in patients with genotype II at diagnosis may improve, while in patients with genotypes ID/DD it is a more constant feature.

Adolescent↗

Deletion polymorphism of the angiotensin I-converting enzyme gene is associated with serum ACE concentration and increased risk for CAD in the Japanese.

BACKGROUND: The angiotensin I-converting enzyme (ACE) is a key component of the renin-angiotensin system thought to be important in the pathogenesis of hypertension and cardiovascular disease. Deletion polymorphism in the ACE gene may be a risk factor for myocardial infarction in the Caucasian population. However, this finding has not yet been investigated in the Japanese population. METHODS AND RESULTS: A 287-bp insertion/deletion polymorphism in intron 16 of the ACE gene was examined by polymerase chain reaction in a cross-sectional study of 100 healthy subjects and 178 patients with coronary artery disease (CAD) (70 angina pectoris, 108 myocardial infarction), whose serum ACE levels were concomitantly measured. Polymorphism of the ACE gene was characterized by three genotypes: two deletion alleles (genotype DD), two insertion alleles (genotype II), and heterozygous alleles (genotype ID). No differences could be detected among the three genotypes for total cholesterol, HDL cholesterol, and body mass index. Serum ACE levels were 11.4 +/- 2.7, 14.5 +/- 3.5, and 16.6 +/- 4.6 IU/mL for genotypes II, ID, and DD, respectively. In the study population, the genotype DD was more closely associated with CAD than the other two genotypes (ID and II). The frequency of deletion alleles was higher (0.58) in the CAD group than in healthy control subjects (0.42) (P < .05). Furthermore, multivessel disease was more strongly associated with deletion alleles than with insertion alleles (P < .05). CONCLUSIONS: A deletion polymorphism of the ACE gene is associated with serum ACE activity and increased risk for CAD in the Japanese.

Adult↗

Hepatitis C virus genotypes in French blood donors.

The prevalence of different hepatitis C virus (HCV) genotypes in HCV infected individuals and the relation between the HCV genotypes and the source of the infection are controversial. The aim of this study was to determine the HCV genotypes in French blood donors. Fifty-one anti-HCV positive blood donors were studied with detectable serum HCV RNA by nested polymerase chain reaction (PCR) using primers derived from the 5' non-coding region. For genotyping HCV, we used a method based on analysis of the restriction fragment length polymorphisms (RFLP) after amplification by PCR of the HCV non-structural 5 (NS5) genome domain. Using this technique, the genotypes of 39 of the 51 blood donors (76%) were determined. Three previously described genotypes were found: 19 blood donors were infected by HCV genotype I (37%), 14 were infected by HCV genotype II (27%), 3 were infected by HCV genotype III (6%), and 3 were coinfected by two genotypes (6%). All three blood donors infected with two different genotypes were intravenous drug abusers. A past history of intravenous drug abuse was more frequent in blood donors with HCV genotype I. However, there was no difference in alanine transaminase (ALT) levels, histological lesions, and RIBA-2 patterns in blood donors infected with either HCV genotype I or HCV genotype II. These findings indicate that most HCV genotypes isolated from French blood donors belong to HCV genotype I and HCV genotype II, and that risk factors for HCV infection may differ for different genotypes of HCV.

Adult↗

Relationship between the response to the angiotensin converting enzyme inhibitor imidapril and the angiotensin converting enzyme genotype.

Insertion (I)/deletion (D) polymorphism of the angiotensin converting enzyme (ACE) gene has been reported to be involved in various cardiovascular diseases. We investigated prospectively whether the response to the ACE inhibitor imidapril varied according to the ACE genotype or plasma ACE activity in Japanese hypertensive patients. The study population consisted of 57 hypertensive patients. After a 4-week observation period, imidapril was administered at a dose of 5 mg/day and blood pressure was measured every 2 weeks for 6 weeks. The plasma ACE activity in patients with the DD or ID genotype was significantly higher than that in patients with the II genotype. Neither the reduction nor the percent reduction in systolic blood pressure was significantly different between patients with either the DD or ID genotype and patients with the II genotype (DD or ID v II, 18.8 +/- 2.4 v 20.2 +/- 3.3 mm Hg; P = NS, 10.9 +/- 1.4 v 11.7 +/- 1.9%; P = NS, respectively). However, both the reduction and the percent reduction in diastolic blood pressure tended to be higher in patients with the II genotype (DD or ID v II, 7.9 +/- 1.2 v 12.4 +/- 2.2 mm Hg; P = .0669, 8.1 +/- 1.2 v 12.4 +/- 2.2%; P = .0569, respectively). The reduction in diastolic blood pressure was inversely correlated with plasma ACE activity (r = 0.301, P = .0253). In conclusion, the response to imidapril in hypertensive patients is determined at least in part by the ACE genotype.

Angiotensin-Converting Enzyme Inhibitors↗

Host-adapted Cryptosporidium spp. in Canada geese (Branta canadensis).

The prevalence and distribution of Cryptosporidium spp. in the fecal droppings of the free-living waterfowl Canada geese were examined at 13 sites in Ohio and Illinois. On the basis of the analysis of the small-subunit rRNA gene by PCR, followed by restriction fragment length polymorphism analysis and DNA sequencing, 49 (23.4%) of 209 fecal specimens collected from 10 sites (76.9%) were positive for Cryptosporidium spp. The following five Cryptosporidium species and genotypes were identified: Cryptosporidium goose genotype I (in 36 specimens), Cryptosporidium goose genotype II (in 9 specimens), Cryptosporidium duck genotype (in 1 specimen), Cryptosporidium parvum (in 4 specimens), and C. hominis (in 2 specimens). Cryptosporidium goose genotype I was the most prevalent parasite and was found at all five Cryptosporidium-positive sites in Ohio and at four of five positive sites in Illinois, followed by Cryptosporidium goose genotype II, which was found at two of five positive sites in Ohio and at four of five positive sites in Illinois. Cryptosporidium goose genotype II was detected for the first time, and it is phylogenetically related to goose genotype I and the duck genotype. All three genotypes have not so far been reported in humans, and their pathogenicity in geese has not been determined. Only 10.2% of the Cryptosporidium-positive specimens had C. parvum and C. hominis. The results of this study indicate that Canada geese might only serve as accidental carriers of cryptosporidia infectious to humans and probably play a minor role in the animal-to-human transmission cycle of the pathogen.

Adaptation, Physiological↗

Renal changes on hyperglycemia and angiotensin-converting enzyme in type 1 diabetes.

Hyperglycemia causes capillary vasodilation and high glomerular capillary hydraulic pressure, which lead to glomerulosclerosis and hypertension in type 1 diabetic subjects. The insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene can modulate risk of nephropathy due to hyperglycemia, and the II genotype (producing low plasma ACE concentrations and probably reduced renal angiotensin II generation and kinin inactivation) may protect against diabetic nephropathy. We tested the possible interaction between ACE I/D polymorphism and uncontrolled type 1 diabetes by measuring glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) during normoglycemia ( approximately 5 mmol/L) and hyperglycemia ( approximately 15 mmol/L) in 9 normoalbuminuric, normotensive type 1 diabetic subjects with the II genotype and 18 matched controls with the ID or DD genotype. Baseline GFR (145+/-22 mL/min per 1.73 m2) and ERPF (636+/-69 mL/min per 1.73 m2) of II subjects declined by 8+/-10% and 10+/-9%, respectively, during hyperglycemia; whereas baseline GFR (138+/-16 mL/min per 1.73 m2) and ERPF (607+/-93 mL/min per 1.73 m2) increased by 4+/-7% and 6+/-11%, respectively, in ID and DD subjects (II versus ID or DD subjects: P=0.0007 and P=0.0005, for GFR and ERPF, respectively). The changes in renal hemodynamics of subjects carrying 1 or 2 D alleles were compatible, with a mainly preglomerular vasodilation induced by hyperglycemia, proportional to plasma ACE concentration (P=0.024); this was not observed in subjects with the II genotype. Thus, type 1 diabetic individuals with the II genotype are resistant to glomerular changes induced by hyperglycemia, providing a basis for their reduced risk of nephropathy.

Adult↗