Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We recently found in a white population that the genes encoding angiotensin-converting enzyme (ACE, I/D polymorphism), alpha-adducin (Gly460Trp), and aldosterone synthase (-344C/T) jointly influence renal function. We therefore investigated in a Chinese population the associations between the serum concentrations of creatinine and uric acid and these three genetic polymorphisms. We genotyped 471 ethnic Han Chinese subjects from 125 nuclear families recruited in northern China via random population sampling (75%) and at specialized hypertension clinics (25%). We performed population-based and family-based association analyses using generalized estimating equations (GEE) and quantitative transmission disequilibrium test (QTDT), respectively, while controlling for covariables. The participants were 39.7 years old and included 235 women (49.9%). The blood pressure measured at the subjects' homes averaged 126/80 mmHg. Mean values were 71 micromol/l for serum creatinine, 111 ml min(-1) 1.73 m(-2) for calculated creatinine clearance, and 236 micromol/l for serum uric acid. With adjustment for covariables, GEE analyses of single genes demonstrated that serum uric acid, but not serum creatinine, was positively associated with the ACE D allele. Serum uric acid concentrations were 15.8 micromol/l (95% confidence interval 3.3-28.2) and 25.7 micromol/l (11.1-40.2) higher in DD homozygotes than in ID and II subjects, respectively. Further GEE analyses of the three genes combined showed that the association between serum uric acid and the ACE polymorphism was confined to carriers of the alpha-adducin Gly and/or aldosterone synthase C alleles. Sensitivity analyses in parents and offspring separately as well as QTDT analyses were confirmatory. Among 114 informative offspring carrying the alpha-adducin Gly allele serum uric acid was significantly and positively associated with the transmission of the ACE D allele (beta=20.7 micromol/l). In conclusion, the present study extends our previous findings on the combined effects of the three candidate genes and supports the concept that these genetic polymorphisms jointly influence renal function.
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PMID:Renal function in relation to three candidate genes in a Chinese population. 1537 62

The molecular mechanisms underlying essential hypertension are not fully elucidated. Although Benazepril is being widely used in antihypertensive medication, the agent is efficacious in only a portion of hypertensive patients. To evaluate the interaction of alpha-adducin gene Gly460Trp and angiotensin I-converting enzyme (ACE) gene I/D polymorphisms in regard to baseline blood pressure (BP) levels and the reductions of blood pressures after Benazepril treatment, we conducted an investigation of 954 Chinese hypertensive patients in Anhui province, China. We found that compared with the baseline systolic BP (SBP) of subjects with one ACE I allele and one alpha-adducin Trp allele, the baseline SBP of those with ACE DD and alpha-adducin Gly/Gly genotypes was significantly higher [Crude: beta(SE) = 7.83(3.09), p = .01; Adjusted: beta(SE) = 5.83(2.83), p = .04]. However, no associations were found between the interaction of ACE I/D and alpha-adducin Gly460Trp polymorphisms and the baseline diastolic BP or the BP response to Benazepril treatment. Our results suggested that the interaction effect of alpha-adducin Gly460Trp and ACE I/D polymorphisms might play a significant role in regulating baseline BP but not BP response to Benazepril.
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PMID:Associations of baseline blood pressure levels and efficacy of Benazepril treatment with interaction of alpha-adducin and ACE gene polymorphisms in hypertensives. 1577 32

Effective blood pressure lowering is essential for prevention of complications of arterial hypertension. Most current guidelines indicate diuretics, beta-blockers, angiotensin converting enzyme inhibitors, calcium channel blockers and angiotensin receptor blockers as main antihypertensive drugs. Genetic polymorphisms underlie pathophysiology of diseases and can affect efficacy of therapy. Method of investigation of pharmacogenetic interrelationships is based on analysis of genes encoding enzymes responsible for metabolism and transport of drugs as well as genes encoding main targets of drug action (receptors). Those polymorphic genes that encode elements of the system of metabolism, adsorption, transport, elimination of drugs, and main receptor systems are considered to be main gene-candidates for pharmacogenetic studies. Some drugs have well known genotypes determining efficacy of therapy as for instance alpha-adducin gene for diuretics. Data on other classes of drugs (e.g. calcium channel blockers) are scanty. Existing information on pharmacogenetic properties of antihypertensive drugs is presented in this review.
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PMID:[Individual sensitivity to antihypertensive drugs: genetic aspects]. 1609 64

Despite the availability of effective antihypertensive drugs, there is a large variation in response to these drugs. This study investigates whether polymorphisms in the angiotensin converting enzyme (I/D), angiotensinogen (M235T), alpha-adducin (G460W), angiotensin II type 1 receptor (1166A/C), or G protein beta(3)-subunit (825C/T) gene modify the mean difference in blood pressure levels among diuretics, beta-blockers, or ACE-inhibitors users. Data were used from the Doetinchem Cohort Study, and blood pressure data were collected from GPs (1987-1997). A marginal generalized linear model (GEE) was used to assess the gene-drug interaction on the mean difference in systolic/diastolic blood pressure. In total, 625 hypertensive individuals were included with a total of 5262 measurements of blood pressure. Only the interaction between diuretic use and the GNB3 825C/T polymorphism was significant (C allele versus TT systolic blood pressure (SBP): 4.33 mmHg [95% CI: 0.14-8.54]). Thus, the mean SBP level among diuretic users may be modified by the GNB3 825C/T polymorphism.
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PMID:Interactions between five candidate genes and antihypertensive drug therapy on blood pressure. 1631 86

Despite the availability of a variety of effective antihypertensive drugs, inadequate control of blood pressure is common in hypertensive patients. The aim of this study was investigate whether the alpha-adducin G460W polymorphism or angiotensinogen M235T polymorphism has an effect on the mean difference in blood pressure in subjects using antihypertensive drugs. Data from the Rotterdam Study, a population-based prospective cohort study in the Netherlands, was used. This study started in 1990 and included 7983 subjects of 55 years and older. Data from three examination rounds were used. Subjects were included when their blood pressure was elevated at 1 or more examinations and/or a diuretic, beta-blocker, calcium antagonist, or ACE inhibitor was used. A marginal generalized linear model was used to assess the drug-gene interaction. In total, 3025 hypertensives were included. No drug-gene interaction on blood pressure levels was found. The mean difference in systolic blood pressure (SBP) between subjects with the W-allele and GG genotype of the alpha-adducin gene was for diuretic users 1.25 mmHg (95% CI:-2.86 to 5.35), for beta-blockers 0.02 mmHg (95% CI:-3.39 to 3.42), for calcium antagonists -0.70 mmHg (95% CI:-5.61 to 4.21), and for ACE inhibitors -3.50 mmHg (95% CI:-9.02 to 2.02). The mean difference in SBP between subjects with the TT and MM genotype was for diuretic users -2.33 mmHg (95% CI:-8.32 to 3.66), for beta-blocker -0.06 mmHg (95% CI:-4.91 to 4.79), for calcium antagonist 0.59 mmHg (95% CI:-5.95 to 7.13), and for ACE inhibitor -2.33 mmHg (95% CI:-9.66 to 5.01). The G460W polymorphism and the M235T polymorphism did not modify the difference in blood pressure levels among subjects who used diuretics, beta-blockers, calcium antagonists, or ACE inhibitors.
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PMID:The influence of the alpha-adducin G460W polymorphism and angiotensinogen M235T polymorphism on antihypertensive medication and blood pressure. 1672 11


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