Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.44 (AGT)
770 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin resistance is a determinant of blood pressure variation and risk factor for hypertension. Because insulin resistance and blood pressure cosegregate in Mexican American families, we thus investigated the association between variations in 9 previously reported hypertension genes (ACE, AGT, AGTRI, ADDI, NPPA, ADDRB2, SCNN1A, GNB3, and NOS3) and insulin resistance. Families were ascertained via a coronary artery disease proband in the Mexican American Coronary Artery Disease Project. Individuals from 100 Mexican American families (n=656) were genotyped for 14 polymorphisms in the 9 genes and all adult offspring and offspring spouses were phenotyped for insulin sensitivity by hyperinsulinemic euglycemic clamp (n=449). AGT M235T and NOS3 A(-922)G and E298D polymorphisms were significantly associated with insulin sensitivity (P=0.018, 0.036, 0.039) but were not significant after adjusting for body mass index. ADD1 G460W was associated with insulin sensitivity only after adjusting for body mass index. The NPPA T2238C and SCNN1A A663T were associated with decreased fasting insulin levels after adjusting for body mass index (P=0.015 and 0.028). In conclusion, AGT, NOS3, NPPA, ADRB2, ADD1, and SCNN1A may well be genetic markers for insulin resistance, and adiposity was a potential modifier for only some gene/trait combinations. Our data support the hypothesis that genes in the blood pressure pathway may play a role in insulin resistance in Mexican Americans.
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PMID:Hypertension genes are genetic markers for insulin sensitivity and resistance. 1569 55

The response of blood pressure to thiazide diuretics (TZDs) differs among individuals. The prediction of the antihypertensive effect of TZDs is important for realizing individualized therapy in the management of hypertension. The aim of this study was to identify the single nucleotide polymorphisms (SNPs) susceptible to the antihypertensive effect of TZDs, particularly focusing on genes related to water-electrolyte absorption in the kidney. Seventy-six outpatients (mean age, 65.4+/-9.0 years) with essential hypertension (EHT) taking TZDs were retrospectively assessed. We defined as responders (R) those whose mean blood pressure was lowered by more than 5 mmHg after the use of TZDs. Forty-eight SNPs in 17 genes (ADD1, GNB3, TSC [SLC12A3], MLR [NR3C2], NCX1 [SLC8A1], WNK1, WNK4, AGT, ACE, AT1 [AGTR1], CYP11B2, ADRB1, ADRB2, ADRB3, ADRA1A, ADRA1B, ADRA2A) were genotyped in the 76 patients. The SNPs in TSC, MLR, NCX1, WNK1, and WNK4 were identified by direct sequencing and those with minor frequencies of greater than 5% were genotyped in this study. The comparison of polymorphism prevalence between R and non-responders (NR) showed significant differences in TSC C1784T (C allele vs. T allele, odds ratio (OR)=3.81, p =0.016, confidence interval (CI): 1.25-11.63) and ADRB3 T727C (Trp64Arg) (T allele vs. C allele, OR=4.59, p =0.005, CI: 1.54-13.68). The blood pressure (BP) in patients homozygous for the major alleles of both TSC C1784T and ADRB3 T727C were significantly reduced by TZD treatment; however, the BP in those homozygous for the minor allele and heterozygous (TSC C1784T: TT+CT; ADRB3 T727C: CC+CT) for both SNPs were not significantly changed after TZD treatment. Both newly detected TSC C1784T and ADRB3 T727C are gene polymorphisms susceptible to the antihypertensive effect of TZDs in patients with EHT. Thus, the prediction of BP reduction by TZDs may be possible by evaluating these two SNPs.
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PMID:The thiazide-sensitive Na(+)-Cl(-) cotransporter gene, C1784T, and adrenergic receptor-beta3 gene, T727C, may be gene polymorphisms susceptible to the antihypertensive effect of thiazide diuretics. 1582 64

Genetic polymorphisms of the renin-angiotensin system (RAS) has been associated with cardiovascular events and the progression of nephropathy in several diseases. The objective of this study was to evaluate a possible association of the genetic polymorphisms of RAS with the development and/or progression of lupus nephritis in a Brazilian population. Seventy-five SLE patients with lupus nephropathy (LN group) were compared to 72 SLE patients without LN (SLE group) and 65 healthy individuals (CONTROL group), of sex and ethnic matched, in a Brazilian population sample. Mean global follow-up was 9 +/- 6 years for lupus without nephropathy and 11 +/- 7 years for lupus nephropathy. Following the extraction of genomic DNA from the leukocytes in the peripheral blood, angiotensin converting enzyme (ACE I/D), angiotensinogen (AGT M(235)T) and angiotensin II type 1 receptor (AGTR1 A(1166)C) genotypes were determined by the polymerase chain reaction. No significant difference of ACE, AGT and AGTR1 genotypes distribution between groups was observed in this study. There was no significant association between the variables of the RAS genotypes and the presence of hypertension in SLE. However, an increased frequency ofDD genotype (ACE I/D) was observed in SLE patients with LN who progressed to CRF compared to healthy controls (DD 60%, DI 26.7%, II 13.3% versus 27.7%, 60% and 12.3%, respectively; chi2 = 6.299, P = 0.0429). In the population studied, there was no influence of the RAS genetic polymorphisms in the development of lupus nephropathy, but the progression to CRF was associated with ACE DD polymorphism.
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PMID:Polymorphisms of the renin-angiotensin system genes in Brazilian patients with lupus nephropathy. 1593 35

To clarify whether the homozygous deletion (DD) genotype of angiotensin-converting enzyme gene ( ACE) is a genetic risk factor for preeclampsia in Japanese women, we performed ACE genotyping in patients with preeclampsia and healthy pregnant women, and analyzed the relationship between preeclampsia and ACE genotype, taking into account some well-known contributing factors for preeclampsia, such as primiparity, positive family history of hypertension, prepregnancy body mass index < 24, and heterozygosity and homozygosity of T235 (MT+TT) genotypes of the angiotensinogen ( AGT) gene. Among all of the subjects, the frequency of the DD genotype was not different between patients with preeclampsia and controls (16% and 12%, respectively). Regarding primiparity, prepregnancy body mass index < 24, and MT+TT genotypes of AGT, no significant differences in the frequency of the DD genotype of ACE were found between patients with preeclampsia and controls, although in a subgroup positive for family history of hypertension, the frequency of the DD genotype tended to be higher in patients with preeclampsia (25%) than in controls (8%; p = 0.061). Carrying the DD genotype may have some influence on the pathogenesis of preeclampsia, perhaps through effects on placental hypoxia or the interaction of hypertensive disease and atherosclerosis, although this influence may not be strong. Additional studies using a larger number of patients and analyses that include other genetic and environmental factors will be necessary to confirm these results.
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PMID:Insertion/deletion polymorphism of the angiotensin-converting enzyme gene and preeclampsia in Japanese patients. 1605 7

Hypertension in pregnancy (HP), one of the most common causes of perinatal deaths, is a multifactorial disease with genetic and environmental factors involved in its etiology. We have carried out molecular epidemiologic research with the purpose of (1) identifying gene variants associated with HP in Japanese women, and (2) analyzing the genetic and environmental factors involved in the pathophysiology of the disease. Self-administered questionnaires were returned by the subjects between 1 and 6 months after delivery. The candidate genetic variants were identified by use of a PCR-RFLP method. T235 of AGT, C1166 of AT1 and Asp298 of NOS3 were respectively associated with HP, although no significant associations were found between the common genetic variants and HP in ACE, FV, MTHFR, B3AR, TNF-A, PAI-1, GSTP1, mEH, and LPL. In analyses using genetic, environmental and lifestyle factors, 5 factors before pregnancy and 4 factors during pregnancy were significantly associated with HP in univariate analysis. Further multivariate analysis revealed 3 factors before pregnancy, i.e. "prepregnancy BMI > or = 24 kg/m(2)", "family history of hypertension" and "TT genotype of AGT", and 2 factors during pregnancy, i.e. "mentally stressful condition" and "salty dishes preferred". Dividing the subjects into 2 subgroups according to whether they possessed "TT genotype of AGT" or not, we identified acquired risk factors before and during pregnancy for HP in each groups. The multivariate analysis identified "mentally stressful condition" as a potent significant risk factor during pregnancy in the former subgroup. However, there were no significant risk factors concerning and "mental stress" in the latter subgroup. Through further exploration of the risk factors associated with HP, we hope to provide useful suggestions about the development of new and effective preventive measures for a range of multifactorial diseases.
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PMID:Genetic and environmental factors associated with the development of hypertension in pregnancy. 1636 2

Recent studies have demonstrated some association between the renin-angiotensin system (RAS) activity and the development and progression of different entities as diabetes mellitus (DM) or chronic allograft nephropathy. To investigate these associations, we studied some gene polymorphisms of RAS in a group of renal transplant recipients. We retrospectively analyzed 42 patients who underwent a primary renal transplantation for 2 years. A subgroup of 23 patients (55%) was diagnosed with postransplant DM in accordance with American Diabetes Association 2001 criteria. We studied two RAS gene polymorphisms: the angiotensin-converting enzyme insertion/deletion (ACE I/D) and angiotensinogen (AGTM235T). Genotyping was performed by DNA purification and amplification with a polymerase chain reaction technique. The distributions of genotypes were ACE DD, ID, II: 33%, 48%, 19%; and AGT TT, MT, MM: 15%, 45%, 40%, respectively. We observed a progressive loss in renal function measured by creatinine clearance (Cockroft) in D-allele carriers (DD+ID) between the first and the second transplantation year: 65.3 +/- 4.3 vs 59.8 +/- 4.6 mL/min (P = 0.02); that was not seen in II patients: 68.8 +/- 4.6 vs 68.4 +/- 4 mL/min (P = 0.87). Fifty percent of D-allele carriers developed DM vs 25% of non-D-allele carriers (P = 0.19). Eighty-three percent of homozygous patients for the AGT-TT allele developed DM vs 35% of non TT patients (P = 0.04). There were no significant differences regarding recipient demographic characteristics, type of donor, number and severity of acute rejections, and immunosuppressant treatment between the groups. In conclusion, ACE D-allele seems to be associated with a poorer kidney graft long-term outcome. ACE D and AGT T alleles may be implicated in glucose metabolism disorders after transplantation.
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PMID:Association of the genetic polymorphisms of the renin-angiotensin system with kidney graft long-term outcome: preliminary results. 1638 15

Polymorphism of the gene encoding components of the renin-angiotensin-aldosterone synthase system (RAAS) represents an area of intense research of cardiovascular disease associations. Numerous studies have addressed the role of RAAS gene polymorphisms in the development and progression of renal disease. Also, it has been reported that patient with ACE (DD) and angiotensinogen AGT (TT) genotypes are associated with chronic allograft dysfunction (CAD). We investigated the effects of gene polymorphisms of the renin-angiotensin-aldosterone system in renal transplant patients (81 males and 50 females; mean age 29.6+/-10.2 years). Genotypes were determined using polymerase chain reaction sequence specific primers and PCR followed by RFLP analysis. Renal allograft recipients with chronic allograft dysfunction had significantly higher frequencies of the MM genotype than those without CAD (P<0.05). The other genetic polymorphisms of the RAAS were not associated with CAD. This study proves that determination of AGT M235T genotype before transplantation may help identify patients who are at risk for chronic renal transplant dysfunction.
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PMID:Polymorphism of the renin-angiotensin-aldosterone system in patients with chronic allograft dysfunction. 1663 53

Left ventricular (LV) remodeling in competitive athletes is a complex phenomenon, in which genetic and environmental determinants are implicated. In recent years, several investigations have demonstrated an association between LV remodeling and the angiotensin-converting enzyme (ACE I/D) and/or angiotensinogen (AGT M/T) polymorphism, with athletes with the DD and/or TT alleles, respectively, showing the greatest increase in LV mass, independent from other determinants. However, the impact of the known genetic determinants on LV remodeling is at present incomplete, and comparative assessment of the genetic and environmental factors, such as the type and intensity of athletic conditioning, suggests that genetic determinants may explain up to one-quarter of the overall variability of LV dimensions. A better understanding of genetic factors may provide an insight into the pathways producing physiological cardiac remodeling, and will be important in understanding the intrinsic nature and clinical significance of the extreme LV morphologic changes observed in highly trained and elite athletes.
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PMID:The genetics of left ventricular remodeling in competitive athletes. 1664

The aim of this study was to determine the frequencies of ACE (I/D), AGT (M235T), AT1R (A1166C) and MTHFR (C677T) polymorphisms in a well-defined (in regards to health and nutritional status and lifestyle) population of young, healthy, exercise-trained subjects (no. 100) from the Campania region of Southern Italy. We also investigated whether there was any correlation between these polymorphisms and biochemical, hematological and hemostatic parameters in this "low-risk" population. Gene polymorphisms were analyzed with the polymerase chain reaction and restriction enzyme analysis. Allele frequencies of the genotypes examined were in Hardy-Weinberg equilibrium and agree with those reported in the Italian population. No associations were found between ACE, AGT, AT1R gene polymorphisms and anthropometric, clinical and laboratory parameters. However, the MTHFR (C677T) polymorphism was significantly associated with lower hemoglobin plasma levels in TT vs. CC + CT females (p < 0.016). This report is the first to describe the frequencies of RAS and MTHFR gene polymorphisms in young, exercise-trained volunteers from Campania and to identify an association between the MTHFR gene polymorphisms and lower hemoglobin plasma levels in young healthy females.
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PMID:RAS and MTHFR gene polymorphisms in a healthy exercise-trained population: association with the MTHFR (TT) genotype and a lower hemoglobin level. 1702 48

There are controversies in reports on the association of polymorphisms in endothelial nitric oxide synthase, angiotensinogen, angiotensin receptor type 1 and angiotensin-converting enzyme genes with an increased risk of developing preeclampsia. We performed a systematic search of published case-control studies through the PubMed database up to January 2006, and report the results of a meta-analysis of polymorphisms investigated in more than five studies: Glu298Asp in eNOS gene (9 analyses involving 1055 patients and 1788 controls), Met235Thr in AGT gene (13 analyses involving 1128 patients and 2278 controls), and intron 16 insertion-deletion polymorphism in ACE gene (10 analyses involving 1121 patients and 1361 controls). Statistically significant associations with preeclampsia were identified for the Met235Thr/AGT polymorphism: OR 1.65 (95% CI 1.19, 2.29) if the polymorphism is considered under the dominant genetic model, and OR 1.54 (95% CI 1.12, 2.11) under the recessive model. For insertion-deletion/ACE polymorphism, statistical significance was demonstrated when the polymorphism was considered under the recessive model: OR 1.51 (95% CI 1.17, 1.94). No single polymorphism was identified as having a major effect.
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PMID:Genetic polymorphisms in vasoactive genes and preeclampsia: a meta-analysis. 1782 85


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