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PubMed2005

Mortality in patients with hypertension on angiotensin-I converting enzyme (ACE)-inhibitor treatment is influenced by the ACE insertion/deletion polymorphism.

BACKGROUND: The response to angiotensin-I converting enzyme (ACE)-inhibitor therapy is highly variable. Residual ACE activity during treatment, potentially modified by the ACE insertion/deletion (I/D) polymorphism, may explain part of this variability. We studied the possible interaction between ACE-inhibitor therapy in patients with hypertension and the ACE I/D polymorphism in incident heart failure and death. METHODS: We studied 3365 hypertensive participants of the population-based Rotterdam Study, without heart failure at baseline for whom ACE-genotyping was successful. Incident heart failure was defined according to established criteria. In addition, total and cardiovascular mortality were studied as endpoints. A Cox regression model with use of ACE-inhibitors defined as time-dependent covariates was used for data-analysis. Interaction was tested in this model assuming an allele-effect relationship. RESULTS: Although we could not demonstrate a beneficial effect of ACE-inhibitors, there was significant interaction between the ACE I/D polymorphism (II-ID-DD) and ACE-inhibitor use in the prediction of total and cardiovascular mortality. Mortality risk associated with treatment increased with the number of D alleles present; e.g. for total mortality in the II genotype group: RR=0.95 (95% CI 0.63-1.45), in the ID genotype group: RR=1.08 (95% CI 0.84-1.38) and in the DD genotype group: RR=1.61 (95% CI 1.18-2.18). No statistically significant interaction was found for incident heart failure. CONCLUSION: The results of our study suggest a relative resistance to ACE-inhibitor therapy in subjects with hypertension and the DD genotype compared to the II genotype, with the ID genotype in an intermediate position.

Aged↗

PubMed1998

Polymorphism of the angiotensin I-converting enzyme gene in diabetic nephropathy in type II diabetic patients with proliferative retinopathy.

Recently, deletion (D)/insertion (I) polymorphism in the Angiotensin I-converting enzyme (ACE) gene has been suggested to be related to the development of diabetic nephropathy in type I diabetes mellitus. This hypothesis, however, remains controversial. Differences in clinical states between patients, especially in glycemic control or duration of diabetes, could be responsible for these contradictory results. In this study we examined the relationship between D/I polymorphism of the ACE gene and diabetic nephropathy in type II diabetic patients who had already developed proliferative retinopathy (n = 45), and were thought to have been in a hyperglycemic state for long enough to develop microangiopathy. The patients were divided into two subgroups: 24 with nephropathy (albumin excretion rate: AER > or = 20 micrograms/min) and 21 without (AER < 20 micrograms/min). There was no difference in the duration of diabetes, HbA1c levels or average blood pressure over the previous year between these subgroups and other clinical characteristics were comparable. Patients without nephropathy exhibited allele I more often than those with nephropathy (p = .025). AER was lowest in genotype II and highest in genotype DD patients but the difference was not statistically significant (p = .07). From these findings, it was concluded that genotype II for the ACE gene could be a marker for reduced risk of diabetic nephropathy.

Case-Control Studies↗

PubMed2006

Insertion/deletion polymorphism of angiotensin I converting enzyme gene and left ventricular hypertrophy in patients with type 2 diabetes mellitus.

INTRODUCTION: Left ventricular hypertrophy (LVH) is a well known risk factor of death from cardiovascular causes. Patients with type 2 diabetes mellitus are at particularly high risk of developing cardiovascular disease, which accounts for 80% of deaths in this group. Type 2 diabetes mellitus is probably related to increased left ventricular mass (LVM). Existing data show that the renin-angiotensin-aldosterone (RAA) system may play a role in the development of LVH. Since the I/D polymorphism of angiotensin-converting enzyme (ACE) gene influences the activity of RAA, it is likely that it could also have an impact on LVH. AIM: To assess the relationship between I/D polymorphism of the ACE gene and the severity of LVH assessed by echocardiography (Echo) in patients with type 2 diabetes mellitus. METHODS: The study group consisted of 103 patients (37 women and 66 men; mean age 60.1+/-9.1 years) suffering from type 2 diabetes mellitus with a mean duration of 9.0+/-6.5 years. BMI, waist-to-hip ratio (WHR), arterial blood pressure, LVM and LVM index (LVM indexed for body surface area [g/m(2)] or height raised to the power 2.7 [g/m(2.7)]) were evaluated. I/D polymorphism of the ACE gene was determined using polymerase chain reaction (PCR). RESULTS: Distribution of I/D polymorphism of the ACE gene in the study group was as follows: genotype II--32.0%, ID--42.7%, DD--25.2% of patients. LVH was diagnosed in 43-71% of patients (depending on criteria used). Distribution of individual genotypes was similar in patients with and without LVH. Genotypes II, ID and DD were observed in 37.3%, 31.4% and 31.4% of patients without LVH (according to the Levy criteria) and in 26.9%, 53.9%, 19.2% in the LVH group, respectively. In persons with DD genotype, when compared to group II, significantly higher values of systolic and diastolic blood pressure were noted (147.7+/-20.2 vs 138.2+/-16.7 mmHg, p=0.03 and 89.4+/-9.7 vs 81.9+/-8.7 mmHg, p=0.004, respectively). CONCLUSIONS: In patients with type 2 diabetes mellitus there is no relationship between I/D polymorphism of the ACE gene and LVH.

Adult↗

PubMed2004

Association of medically unexplained fatigue with ACE insertion/deletion polymorphism in Gulf War veterans.

Genes associated with muscle metabolism and physical endurance were evaluated for variants that may contribute to the etiology of medically unexplained severe and chronic fatigue. Subjects included 49 Gulf War veterans and 61 nonveterans with chronic fatigue syndrome (CFS) or idiopathic chronic fatigue (ICF) and 30 veterans and 45 nonveterans who served as healthy controls. Increased risk for CFS/ICF was associated with alterations of the insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme gene within the Gulf War veteran sample only. The I allele frequency was decreased in affected versus unaffected veterans (0.15 versus 0.48; odds ratio [OR], 5.08; 95% confidence interval [CI], 1.97-13.35; P < 0.0001). Correspondingly, the II genotype was decreased fourfold in affected veterans (0.08 versus 0.35; OR = 5.87; 95% CI: 1.21-28.36; P = 0.02), and the DD genotype was increased twofold (0.78 versus 0.39; OR, 5.4; 95% CI, 1.6-18.4; P = 0.007). Veterans with the DD genotype were eight times more likely to develop CFS/ICF than were those with the II genotype (OR, 8.30; 95% CI, 1.50-56.09; P = 0.009).

Fatigue Syndrome, Chronic↗

PubMed2006

Association of lipoprotein receptor, receptor-associated protein, and metabolizing enzyme gene polymorphisms with gallstone disease: A case-control study.

INTRODUCTION: To identify high risk alleles for gallstone disease, we analyzed association of LDLRAvaII, LRPAP1 insertion/deletion, CETPTaqI B, and LPLHindIII polymorphisms with gallstone disease. METHODS: In DNA samples of 214 gallstone patients and 322 age and sex matched controls, specific region containing polymorphisms was PCR amplified and digested with restriction enzymes except for LRPAP1 insertion/deletion polymorphism. RESULTS: LRPAP1 gene insertion/deletion polymorphism was found to be significantly associated with gallstone disease. Genotype II was conferring significant risk for gallstone disease in females only (P=0.019; OR 2.577, 95% CI 1.144-5.806). LDLRAvaII, CETPTaqI B, and LPLHindIII polymorphisms were not found to be associated with gallstone disease either at genotype or allele level. CONCLUSIONS: LRPAP1, II genotype carrier females may have increased risk for gallstone disease. On the other hand, LDLR AvaII, CETP TaqI B, and LPL HindIII polymorphisms may not be associated with gallstone disease.

Journal Article↗

PubMed2001

Loss of renal function following bone marrow transplantation: an analysis of angiotensin converting enzyme D/I polymorphism and other clinical risk factors.

Chronic renal failure is an acknowledged late complication of BMT. It is related to the intensive chemotherapy, radiation and supporting medications. Polymorphism in the angiotensin converting enzyme (ACE) gene is associated with progression of nephropathy caused by diabetes and IgA nephropathy. We sought to determine whether ACE genotype and other clinical factors were associated with loss of renal function after BMT. We determined the genotype of 106 adult allogeneic BMT recipients, who received a similar preparative regimen, survived 1 year, and had assessment of renal function up to 3 years after BMT. We found that the distribution of genotypes was similar to the general population; 29%, 51%, and 20% for the DD, DI, and II genotypes, respectively. There was no statistical difference in patient survival between the three groups. Among all patients, the average creatinine clearance declined from 124 (95% CI 117, 131) to 89 (95% CI 78, 100) ml/min over the 36 months after BMT. Decline in renal function over time was less for patients with the DD compared to the II genotype (P = 0.040). Renal function in patients with the DD genotype was also better than those with the DI genotype, but this was of borderline statistical significance (P = 0.055). Renal shielding reduced decline in renal function compared to no shielding (P = 0.026). We conclude that the ACE genotype does not seem to influence survival, but the DD genotype may be protective against renal injury after BMT. Furthermore, we confirm that renal shielding during TBI reduces the renal injury after BMT.

Adolescent↗

PubMed2005

Angiotensin-converting enzyme polymorphism in healthy young subjects: relationship to left ventricular mass and functions.

OBJECTIVES: Angiotensin-converting enzyme (ACE) is a key enzyme in the production of angiotensin II and thus may participate in the modulation of cardiac growth. The cloning of the ACE gene has made it possible to identify a deletion (D)-insertion (I) polymorphism that appears to affect the level of serum ACE activity. The aim of the study is to analyse the ACE gene I/D polymorphisms in healthy young subjects and to evaluate its relationship to left ventricular mass and functions. METHODS: 38 women and 40 men (mean age 21.1 +/- 1.7 and 21.4 +/- 1.7 years) were studied. They underwent complete echocardiographic assessment and analysis of ACE insertion (I) and deletion (D) allele frequencies in peripheral blood by polymerase chain reaction. Thickness of interventricular septum (IVS) and posterior wall (LVPW) and left ventricular mass (LVM) and LVM index (LVMI) were measured by M-mode. Left ventricular ejection fraction (LVEF) was calculated by Simpson's method. RESULTS: There was no statistically significant difference among the DD, DI and II genotypes, concerning age, body mass index, heart rate, systolic and diastolic blood pressures.The thickness of IVS (9.5 mm), LVPW (9.0 mm), LVM (204.5 g) and LVMI (105.5 g/m2) in DD genotypes were higher than both DI (8.3 mm; 8.1 mm; 168.1 g; 90.9 g/m2) and II genotypes (8.2 mm; 7.0 mm; 141.7 g; 77.8 g/m2) in men, but not in women. LVEF among the 3 genotypes were not statistically different. CONCLUSION: Our findings suggest that left ventricular hypertrophy is partially determined by genetic disposition especially in men but not in women.

Adult↗

PubMed2006

[Acoustic evoked potentials, serotonin transporter gene polymorphism and some psychopathological and psychological features in patients with schizophrenia and their relatives].

Serotonin transporter gene is known to be implicated with various psychological and psychiatric phenotypes. The present study aimed at searching for relationship of the gene polymorphism 5-HTTLPR to personality traits and P300 wave in patients with schizophrenia (n = 71) and their non-psychotic relatives (n = 74). To reduce an influence of the P300 amplitude range, which may vary widely in population, subjects have been divided into 2 groups: with amplitude higher (group m+) and lower (group m-) than a mean sample value. Between-amplitude differences were highly significant (p < 0.0001) for all the leads. The groups were similar by age, sex ratio and emotional level measured with personality inventories. When compared by 5-HTTLPR genotype, mean P300 amplitude values were similar in the group m-. In the group m+, significant differences for this component were found between the II genotype and the ss genotype at frontal (p = 0.02) and central (p = 0.005) leads, with the ss genotype subjects having the lowest amplitude. Subjects with the ss genotype in this group as compared to those with the II genotype were also featured by higher anxiety- and depression-related personality traits in relatives and marked clinical symptoms related to anxiety and depression in patients. The fact that association between 5-HTTLPR polymorphism and with P300 amplitude as well as personality traits was found only in the group with higher amplitudes, but not in the group with lower amplitudes, may be partly explained by the assumption that these groups represent different phenotypes. Subjects with inherent lower amplitude are thought to have reduced ability of behavior self-regulation. In conclusion, 5-HTTLPR polymorphism seems to contribute to information processing related to P300 generation and to anxiety and depression traits in patients with schizophrenia and their relatives.

Adult↗

PubMed2004

[Relationships between polymorphisms of angiotensin-converting enzyme and methylenetetrahydrofolate reductase genes and genetic susceptibility to pregnancy induced hypertension].

OBJECTIVE: To study the relationships between polymorphisms of angiotensin-converting enzyme (ACE) gene and methylenetetrahydrofolate reductase (MTHFR) gene and pregnancy induced hypertension (PIH). METHODS: Ninety-nine PIH patients (PIH group), including 21 mild cases, 24 moderate cases and 54 severe cases and 54 normal pregnant women (control group) were recruited. The polymorphism of ACE gene was detected by PCR, and that of MTHFR gene was detected by PCR-RFLP. RESULTS: In PIH group, the frequencies of genotypes II, ID, and DD of ACE gene were 20.2%, 37.4% and 42.4% respectively, the frequencies of genotypes CC, CT, and TT of MTHFR gene were 53.5%, 31.3% and 15.2% respectively. There existed significant difference between genotypes DD, CT and D allele in PIH group and control group. Compared to mild PIH group, the frequencies of genotypes DD and CT in severe PIH group were significantly higher. The susceptibility to PIH in individuals with genotypes CC + DD was 2.648 times that of the controls. However, individuals with genotypes CT + II and CC + II were less susceptible to PIH in comparison to the controls. Logistic regression analysis showed that genotype DD and D allele were associated with PIH, genotype CT was associated with severe PIH. CONCLUSION: Genotypes DD and CT may be the risk factors of PIH; genotype II may have a protective effect against PIH. There may exist some interaction between polymorphisms of ACE gene and MTHFR gene in the pathogenesis of PIH.

Adult↗

PubMed2005

Comparison of the effect of enalapril and losartan in conjunction with surgical coronary revascularisation versus revascularisation alone on systemic endothelial function.

OBJECTIVES: To investigate the effect of enalapril, losartan, and surgical coronary revascularisation on endothelial function, and the role of the angiotensin converting enzyme (ACE) insertion (I)/deletion (D) polymorphism. DESIGN: Randomised, controlled, blinded end point study. SETTING: University tertiary referral cardiac centre. PATIENTS AND INTERVENTIONS: 49 men awaiting coronary artery bypass grafting (CABG) were randomly assigned to treatment with losartan, enalapril, or control for two months before and three months after surgery. MAIN OUTCOME MEASURES: Endothelial function was blindly analysed by brachial artery flow mediated dilatation (FMD) and ACE I/D genotype was determined. RESULTS: FMD was impaired at baseline (1.0-1.7%) and after five months had improved to 5.2% with enalapril (p = 0.015), 5.0% with losartan (p = 0.0004), and 3.0% with CABG alone (p = 0.05). Patients with the II genotype had lower baseline FMD than those with DI or DD (0.1% v 1.7%, p = 0.038) and after enalapril or losartan treatment had greater improvement in FMD (mean (SEM) 7.1 (1.1)%) than patients with DI (3.1 (1.3)%, p = 0.024) or DD genotype (3.1 (1.1)%, p = 0.02). CONCLUSIONS: Enalapril and losartan, with surgical coronary revascularisation, significantly improve systemic endothelial function. Revascularisation alone produces a quantitatively smaller, but still significant, improvement. The ACE genotype significantly modulates this response. Patients with the II genotype have a more pronounced impairment in endothelial function at baseline and a greater improvement in response to treatment with these agents.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2000

Interactions between angiotensin-I converting enzyme insertion/deletion polymorphism and response of plasma lipids and coronary atherosclerosis to treatment with fluvastatin: the lipoprotein and coronary atherosclerosis study.

OBJECTIVES: Our objectives were to determine whether angiotensin-1 converting enzyme (ACE) insertion/deletion (I/D) polymorphism was associated with the severity of coronary artery disease (CAD) and its progression/regression in response to fluvastatin therapy in the Lipoprotein and Coronary Atherosclerosis Study (LCAS) population. BACKGROUND: Genetic factors are involved in susceptibility to CAD. Angiotensin-1 converting enzyme I/D polymorphism, which accounts for half of the variance of plasma and tissue levels of ACE, has been implicated in susceptibility to CAD and myocardial infarction (MI). METHODS: Angiotensin-1 converting enzyme genotypes were determined by polymerase chain reaction (PCR). Fasting plasma lipids were measured and quantitative coronary angiograms were obtained at baseline and 2.5 years following randomization to fluvastatin or placebo. RESULTS: Ninety-one subjects had DD, 198 ID and 75 II genotypes. The mean blood pressure, minimum lumen diameter (MLD), number of coronary lesions and total occlusions were not significantly different at baseline or follow-up among the genotypes. There was a significant genotype-by-treatment interaction for total cholesterol (p = 0.018), low-density lipoprotein cholesterol (LDL-C) (p = 0.005) and apolipoprotein (apo) B (p = 0.045). In response to fluvastatin therapy, subjects with DD, compared with those with ID and II genotypes, had a greater reduction in total cholesterol (19% vs. 15% vs. 13%), LDL-C (31% vs. 25% vs. 21%) and apo B (23% vs. 15% vs. 12%). Definite progression was less (14%) and regression was more common (24%) in DD as compared with those with ID (32% and 17%) and II (33% and 3%) genotypes (p = 0.023). Changes in the mean MLD and lesion-specific MLD also followed the same trend. CONCLUSIONS: Angiotensin-1 converting enzyme I/D polymorphism is associated with the response of plasma lipids and coronary atherosclerosis to treatment with fluvastatin. Subjects with DD genotype had a greater reduction in LDL-C, a higher rate of regression and a lower rate of progression of CAD.

Adult↗

PubMed1999

Pharmacogenetic analysis of the effect of angiotensin-converting enzyme inhibitor on restenosis after percutaneous transluminal coronary angioplasty.

Angiotensin-converting enzyme (ACE) inhibitors are reported to prevent neointimal formation after balloon injury in animal models, but in most prospective studies in humans, ACE inhibitors failed to prevent restenosis after percutaneous transluminal coronary angioplasty (PTCA). The ACE genotype assigned by an insertion/deletion (I/D) polymorphism is known to affect the potency of ACE inhibitors in several renal diseases. The authors attempted to clarify whether the effect of ACE inhibitors on restenosis might be modified by the ACE genotype. A total of 126 patients was randomly and prospectively assigned to the control group and the imidapril group. In the imidapril group, patients received 5 mg imidapril daily, starting 1 day before PTCA and continuing for 3 to 6 months. Forty-six control (65 vessels) and 32 imidapril patients (43 vessels) completed the study. The minimal lumen diameter before and after the procedure did not differ significantly among the groups with the three genotypes (II, ID, and DD) in both the control and imidapril groups. Late luminal loss during the follow-up period was not related to the ACE genotype in the control group but was significantly related in the imidapril group (II, 0.63+/- 0.19 mm; ID + DD, 1.12+/-0.14 mm, p<0.05). Furthermore, in the II genotype, imidapril significantly reduced late loss and restenosis rate as defined by most of the frequently used definitions. In conclusion the ACE I/D polymorphism may influence the effect of ACE inhibitors in preventing restenosis after PTCA.

Aged↗

PubMed1995

Genomic characterization of hepatitis C virus isolates from Argentina.

Thirty-three Argentinian patients infected with hepatitis C virus (HCV) were studied for viral genotyping. The patients included 10 hemophiliac and 4 polytransfused children and 19 adults: 3 polytransfused, 7 dialyzed and 9 sporadic cases. Core-based genotyping permitted the classification of 31 samples. Genotypes II, I and V were the most frequent: 21 (63.6%), 16 (48.4%) and 10 (30.3%) of the 33 patients, respectively. Only one polytransfused patient carried genotype IV. Genotype II was detected in 7 out of 9 sporadic cases. Thirteen patients (39.3%) were coinfected with two genotypes, and 2 others were coinfected with three genotypes. The remaining 2 samples which could not be typed were characterized following the restriction fragment length polymorphism (RFLP) method, and were classified as type 1. One of these had two consecutive transitional mutations in the 5' untranslated region (5' UTR).

Adult↗

PubMed2005

Deletion allele of angiotensin-converting enzyme is associated with increased risk and severity of bronchopulmonary dysplasia.

OBJECTIVE: To explore whether the deletion (D) allele of angiotensin-converting enzyme (ACE) is associated with the risk or severity of bronchopulmonary dysplasia (BPD) among very low birth weight (BW) infants. STUDY DESIGN: Infants with a BW < or = 1250 g were prospectively recruited. The D and I (insertion) alleles of ACE were determined using a polymerase chain reaction followed by restriction fragment length polymorphism analysis. RESULTS: Infants with DD/DI genotype of ACE had a (mean +/- SD) birth weight (938 +/- 204 g vs 925 +/- 196 g) and gestational age (28 +/- 3 weeks vs 28 +/- 2 weeks), similar to infants with II genotype of ACE (P > .05). Infants with DD/DI genotype of ACE were more likely to have BPD than infants with II genotype (47% vs 22%, P = .025). Among infants with BPD, ACE DD/DI genotype was more common among infants with moderate or severe BPD compared with infants with mild BPD (74% vs 26%, P = .012). The number of D alleles of ACE correlated directly and positively with the severity of BPD (R = 0.23, P = .045). CONCLUSION: The D allele of ACE is associated with an increased risk and severity of BPD among preterm infants.

Bronchopulmonary Dysplasia↗

PubMed1996

Common DNA polymorphisms at the lipoprotein lipase gene. Association with severity of coronary artery disease and diabetes.

BACKGROUND: DNA variants of the lipoprotein lipase gene are associated with changes in lipid metabolism similar to those in diabetes and may relate to the development of atherosclerotic lesions, particularly premature lesions. METHODS AND RESULTS: To determine whether lipoprotein lipase gene variants are relevant to ongoing atherogenesis, we explored relationships between two common lipoprotein lipase gene polymorphic markers, Pvu II at intron 6 and HindIII at intron 8; the severity of coronary artery disease (CAD); and lipid variables in 475 white patients 65 years of age or younger. We assessed CAD severity as the number of significantly stenosed (> 50% luminal obstruction) major coronary arteries at angiography and by the Green Lane coronary score. We found a significant association between the Pvu II polymorphism and the number of significantly diseased vessels (P = .0099) and coronary score (P = .028), with the Pvu II(-) alleles associated with less severe disease. The HindIII polymorphism was not associated with severity but had an additive effect with the Pvu II polymorphism. There was a close relationship between the Pvu II(+/+) genotype and the presence of diabetes (P = .0025), with an OR of 3.12 (95% CI, 1.30 to 7.49) compared with the Pvu II(-/-) genotype. The interaction between these polymorphisms and CAD severity (rather than occurrence) was independent of the levels of triglycerides and HDL cholesterol and of other lipid variables. There was also a dosage-dependent relationship between the Pvu II polymorphism and levels of triglyceride. The Pvu II(-) allele was associated with low levels and variances of triglycerides. CONCLUSIONS: We conclude that the lipoprotein lipase Pvu II polymorphism is significantly associated with CAD severity and with type II diabetes in CAD patients, independent of changes in circulating lipid levels. These findings may be relevant to mechanisms mediating atherogenesis.

Aged↗

PubMed2000

The insertion/deletion polymorphism of the angiotensin-converting enzyme gene determines coronary vascular tone and nitric oxide activity.

OBJECTIVES: We investigated whether the insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene modulates vasomotor tone and endothelial function. BACKGROUND: The deletion allele of the ACE I/D polymorphism has been associated with increased incidence of cardiovascular pathology. The risk is synergistically increased in patients who also possess the C allele at position 1,166 of the angiotensin type I (AT1) receptor gene. METHODS: In 177 patients with coronary atherosclerosis or its risk factors, we investigated endothelial function with intracoronary acetylcholine (ACH), endothelium-independent smooth muscle function with sodium nitroprusside (SNP) and basal nitric oxide activity with L-NG monomethyl arginine. RESULTS: Compared with ACE II genotype, patients with the ACE DD genotype had lower coronary microvascular and epicardial responses with SNP (coronary blood flow increase 196 +/- 26% vs. 121 +/- 11%, p = 0.003, and diameter increase 21.9 +/- 2% vs. 17 +/- 1%, p = 0.03, ACE II vs. DD, respectively). L-NG monomethyl arginine induced greater constriction in patients with the ACE DD compared with ACE II genotype (coronary blood flow -10 +/- 4% vs. 11 +/- 5%, p = 0.003, ACE DD vs. II and diameter constriction -6.3 +/- 1.2% vs. -1.9 +/- 1.2%, p = 0.01, respectively, in patients with atherosclerosis). No difference in ACH-mediated vasomotion was detected between the three ACE genotypes. The AT1 receptor polymorphism did not influence responses to either SNP or ACH. CONCLUSIONS: Patients possessing the D allele of the ACE gene have increased vascular smooth muscle tone. The enhanced tone appears to be counterbalanced by an increase in basal nitric oxide activity in patients with atherosclerosis.

Acetylcholine↗

PubMed2003

Tumour necrosis factor receptor type II 196M/R genotype correlates with circulating soluble receptor levels in normal subjects and with graft-versus-host disease after sibling allogeneic bone marrow transplantation.

BACKGROUND: A single nucleotide polymorphism in the tumor necrosis factor type II receptor (TNFRII) gene, codon 196, results in the substitution of arginine (R allele) for methionine (M allele). The 196R allele is reportedly associated with an increased susceptibility to autoimmune disease, and donor 196R allele carriage correlates with increased severity of acute graft-versus-host disease (GVHD) after matched unrelated bone marrow transplantation (BMT). METHODS: We investigated the impact of donor and recipient TNFRII genotype on GVHD incidence and severity among 104 adult recipients of myeloablative sibling BMTs. RESULTS: 196R allele frequency was 0.28 among recipients, donors, and controls. There was an increased incidence of acute GVHD among 196R-positive recipients (odds ratio [OR] 3.6, P=0.05). This association was confirmed in multivariate analysis (relative risk 4, P=0.04), correcting for previously established clinical and genetic risk factors. Donor 196R homozygosity was associated with an increased incidence of extensive chronic GVHD (OR 18.5, P=0.02). This association was also confirmed in multivariate analysis (OR 11, P=0.02). To investigate the functional impact of the TNFRII 196 M/R polymorphism, 79 volunteer blood donors were genotyped at this locus, by polymerase chain reaction and single-strand conformational polymorphism analysis, and plasma soluble TNFRII (sTNFRII) levels were measured by ELISA. Mean plasma sTNFRII levels (pg/mL: +/-SEM) were 1224 (+/-26) and 1063 (+/-65) for 196M-postive (196 M homozygous or heterozygous) individuals and 196R homozygotes, respectively (P=0.02). CONCLUSIONS: Because sTNFRIIs can act as TNF antagonists, the association between recipient and donor TNFRII 196R allele status and acute or extensive chronic GVHD incidence, respectively, may reflect reduced circulating sTNFRII.

Adolescent↗

PubMedDate not supplied

[Viral C hepatitis in patients with end stage renal disease. II. Viral genotypes].

BACKGROUND: The hepatitis C virus infection is highly prevalent in patients on chronic dialysis. There are more than 10 variants of the hepatitis C virus, with 55 to 72% of identity among them at the amino acid level. However, we do not know the specific genotype in dialysis patients in Mexico. Thus, the aim of the present study was to know the specific genotypes of the C virus in infected dialysis patients, to know the distribution of genotypes in the different dialysis techniques and to know the relation between genotype and hepatic disease stage. METHODS: We performed a prospective, transversal and comparative study in patients in dialysis in three hospital centers in the south of Mexico City. The presence of C-type hepatitis infection was assessed by ELISA II and qualitative RT-PCR in blood samples. The genotype of the hepatitis C virus was determined by analysis of the restriction pattern of the RT-PCR product using Mva I, Hinf I, BstU I and ScrF I restriction enzymes. Variables analyzed were: age, gender, etiology of renal failure, kind and time in substitutive therapy, transfusion and hepatitis history, liver function test, blood urea, serum creatinine and blood cell count. RESULTS: We studied 235 dialysis patients that were divided following their dialysis modality into: 132 in continue ambulatory peritoneal dialysis (CAPD), 17 in CAPD, but with history of hemodialysis (PD/HD) of at least one month and 86 on hemodialysis (HD). The hepatitis infection was detected in 24 of the 235 patients (CAPD = 4.5%, PD/HD = 41.1% and HD = 12.7%; p < 0.001). The most common genotype was 1B (12/24), followed by 1A and 2A (4/24 each one), and finally by 2B and 2C (2/24 each one). We detected no patients with genotypes 3 to 6. The patients with 2A genotype were older than those infected with 1A (p < 0.05). History of surgery, transfusions, and hepatitis was similar in all genotypes. Finally the time in dialysis was longer in patients with 2A genotype than others (2A = 60.5 +/- 71.5 months, vs. 1A = 11.5 +/- 11.3, 1B = 26 +/- 26.4 y 2B/C = 17.5 +/- 13.4), but the difference did not reach statistical significance. The genotype distribution between dialysis techniques showed that 1B genotype was the most frequent in all modalities. The 1A genotype was present in similar proportions in patients of the three dialysis groups, the 2C genotype was present only in patients with CAPD. Finally, the 2B was only found in hemodialysis patients. DISCUSSION: The assessment of viral genotype revealed that 1B is the most common genotype in patients on chronic dialysis in Mexico City. The fact that the 1B and 1A genotypes were the most common types in our dialysis population suggest that transmission was similar to the general population, that is, probably by blood transfusions.

Adult↗