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At least 1,135 records · Page 63Linked to original sources
PubMed2005

Overexpression of osteopontin in rheumatoid synovial mononuclear cells is associated with joint inflammation, not with genetic polymorphism.

OBJECTIVE: Osteopontin (OPN) is thought to play an important role in rheumatoid synovitis. We investigated the expression of OPN in rheumatoid synovial fluid mononuclear cells (SFMC) and its potential association with genetic polymorphism of the OPN gene and joint inflammation in rheumatoid arthritis (RA). METHODS: 1. The expression of OPN mRNA in peripheral blood mononuclear cells (PBMC) and SFMC of patients with RA was analyzed quantitatively by real-time polymerase chain reaction (PCR). Results were analyzed in paired PBMC and SFMC and control PBMC. 2. Six single nuclear acid polymorphisms of the OPN gene were genotyped in a cohort of 192 Chinese patients with RA and controls (n = 288) by restriction fragment length polymorphism PCR or direct DNA sequencing. 3. SF derived from RA patients was examined for the stimulating effect on mRNA expression of the OPN gene in PBMC. RESULTS: The expression of OPN gene was significantly increased in SFMC and, to a lesser degree, in PBMC of patients with RA compared to control PBMC (p < 0.01). However, the prevalence of OPN genotype and allele frequencies at the selected positions did not differ significantly between RA patients and the control group (p > 0.05). Further characterization indicated that SF known to contain a variety of proinflammatory factors significantly stimulated mRNA expression of OPN in PBMC obtained from RA patients or healthy controls. CONCLUSION: Overexpression of OPN mRNA in SFMC is associated with proinflammatory factors produced in inflamed joints, but not with OPN genetic polymorphisms. OPN gene polymorphisms do not correlate with susceptibility to RA.

Adult↗
PubMed1998

The effects of genetic polymorphisms of CYP2C9 and CYP2C19 on phenytoin metabolism in Japanese adult patients with epilepsy: studies in stereoselective hydroxylation and population pharmacokinetics.

PURPOSE: The aim of this study was to clarify the effects of genetic polymorphisms of cytochrome P450 (CYP) 2C9 and 2C19 on the metabolism of phenytoin (PHT). In addition, a population pharmacokinetic analysis was performed. METHODS: The genotype of CYP2C9 (Arg144/Cys, Ile359/Leu) and CYP2C19(*1, *2 or *3) in 134 Japanese adult patients with epilepsy treated with PHT were determined, and their serum concentrations of 5-(4-hydroxyphenyl)-5-phenylhydantoin (p-HPPH) enantiomers, being major metabolites of PHT, were measured. A population pharmacokinetic analysis (NONMEM analysis) was performed to evaluate whether genetic polymorphism of CYP2C9/19 affects the clinical use of PHT by using the 336 dose-serum concentration data. RESULTS: The mean maximal elimination rate (Vmax) was 42% lower in the heterozygote for Leu359 allele in CYP2C9, and the mean Michaelis-Menten constants (Km) in the heterozygous extensive metabolizers and the poor metabolizers of CYP2C19 were 22 and 54%, respectively, higher than those without the mutations in CYP2C9/19 genes. (R)- and (S)-p-HPPH/PHT ratios were lower in patients with mutations in CYP2C9 or CYP2C19 gene than those in patients without mutations. CONCLUSIONS: Although the hydroxylation capacity of PHT was impaired with mutations of CYP2C9/19, the impairment was greater for CYP2C9. In view of the clinical use of PHT, two important conclusions were derived from this population study. First, the serum PHT concentration in patients with the Leu359 allele in CYP2C9 would increase dramatically even at lower daily doses. Second, the patients with CYP2C19 mutations should be treated carefully at higher daily doses of PHT.

Aryl Hydrocarbon Hydroxylases↗
PubMed2002

A review of genetic polymorphisms and prostate cancer risk.

In this study, we review a variety of genetic polymorphisms that may have an etiologic role in prostate cancer. We include associations identified in molecular epidemiology studies and the consistency of findings reported to date. Suggestions for further research are also offered. For the purposes of this review, we identified relevant articles through a MEDLINE search for the period of January 1987 through March 2001. The searches were limited to articles published in English. Medical subject headings were used to scan titles, abstracts, and subject headings in the databases using the keywords "prostate neoplasms," "genetics," and "polymorphisms."

Genetic Linkage↗
PubMed2003

Reproductive factors, glutathione S-transferase M1 and T1 genetic polymorphism and breast cancer risk.

We conducted a hospital-based case-control study to evaluate the interactive effect of reproductive factors and glutathione S-transferase (GST) M1 and T1 genetic polymorphisms in individual susceptibility to breast cancer. The study population consisted of 189 incident breast cancer cases and 189 age-matched controls with no known malignant diseases. GSTM1/T1 genotypes were determined by a multiplex polymerase chain reaction (PCR) method, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by conditional logistic regression model. The parity factors were grouped as (1) high-risk status defined as nullipara or para with experience of first full-term pregnancy (FFTP) at or over 30 years, and (2) low-risk status defined as para with experience of FFTP under 30 years. A significant multiplicative interaction was observed between GSTM1 and GSTT1 null genotypes and high-risk status of parity factor in all women and in premenopausal women (P < or = 0.01), but not in postmenopausal women (P > 0.05). The interaction between the combined genotypes of GSTM1 and GSTT1 and status of parity factor was also significant in all women and in premenopausal women (P < 0.01). Our findings suggest that genetic polymorphisms GSTM1/T1 could modify estrogen-related breast cancer risk.

Breast Neoplasms↗
PubMed2003

Genetic polymorphism of cytochrome P450 enzymes in Asian populations: focus on CYP2D6.

Published studies demonstrate that significant ethnic differences can exist in the metabolism of some drugs. These differences are caused by cytochrome P450 polymorphisms and result in the potential for wide interpatient and interethnic variability in adverse events. One of the most common of these cytochrome P450 polymorphisms is related to the CYP2D6 isozyme. Many classes of commonly used drugs are metabolized by CYP2D6, creating the potential for significant adverse events. Due to the variety of genetic polymorphisms among Asian populations, this article focuses on this group rather than on other ethnic populations and discusses the clinical importance of genetic polymorphisms with regard to potential drug interactions. Polymorphism of CYP2D6 can either increase the rate of drug elimination (ultrametabolizers, leading to faster metabolic clearance potentially resulting in reduced effectiveness and need for higher doses) or decrease drug metabolism (poor metabolizers, which may increase the potential for drug interactions and adverse events). Although the CYP2D6 poor metabolizer phenotype is less frequent in Asian than in Western populations (e.g. about 1% in Thai, Chinese and Japanese populations and up to 4.8% in Indians versus 5-10% in Caucasians), the increased prevalence of the CYP2D6*10 allele in Asians does have an impact on drugs metabolized by CYP2D6. Enzyme activity is reduced, potentially increasing circulating drug doses and increasing the risk for drug interactions. Thus, in Asian populations it may be important to optimize pharmacotherapy either by assessing patients' CYP2D6 genotype, or by prescribing medications that are not metabolized by this isozyme.

Alleles↗
PubMed1998

[Genetic polymorphisms as risk factors for coronary artery disease].

The acute myocardial infarction is a multi factor disease, and various risk factors participate in its occurrence and progression. Recently, many investigators have paid their attention to the genetic polymorphisms as new risk factors for coronary artery disease. These include the polymorphisms or mutations of the gene which relates to hypertension, diabetes, the platelet function, the property of the blood vessel, the blood coagulation fibrinogenolysis system, and serum lipids. The tendency toward the occurrence and progression of coronary artery disease might be decided genetically by combining these genetic polymorphisms.

Angiotensinogen↗
PubMed2004

Genetic polymorphisms in UDP-glucuronosyltransferases and glutathione S-transferases and colorectal cancer risk.

Colorectal cancer (CRC) is one of the most common malignancies in the Western world showing an increasing incidence, and has been associated with genetic and lifestyle factors. Individual susceptibility to CRC may be due partly to variations in detoxification capacity in the gastrointestinal tract. Genetic polymorphisms in detoxification enzymes may result in variations in detoxification activities, which subsequently might influence the levels of toxic/carcinogenic compounds, and this may influence the risk for CRC. To determine whether genetic polymorphisms in detoxification enzymes predispose to the development of CRC, 371 patients with sporadic CRC and 415 healthy controls were genotyped for polymorphisms in the important detoxification enzymes UDP-glucuronosyltransferase UGT1A1, UGT1A6, UGT1A7 and UGT1A8, and glutathione S-transferase GSTA1, GSTM1, GSTP1 and GSTT1. Patients and controls were all of Caucasian origin. DNA was isolated from either blood or tissue and tested by polymerase chain reaction followed by restriction fragment length polymorphism analyses. Logistic regression analyses showed significant age- and gender-adjusted risks for CRC associated with variant genotypes of UGT1A6 [OR 1.5, 95% (confidence interval) CI 1.03-2.3] and UGT1A7 (OR 2.4, 95% CI 1.3-4.6), whereas no associations were found between CRC and the other polymorphic genes as mentioned above. In conclusion, the data suggest that the presence of variant UGT1A6 and UGT1A7 genotypes with expected reduced enzyme activities, might enhance susceptibility to CRC.

Adult↗
PubMed2001

[Genetic polymorphism of blood group and erythrocyte enzymes in three ethno-territorial groups of the northern European part of Russia].

Using the data on five red cell markers (AB0, PGM1, ACP1, GLO1, and ESD) polymorphisms, the population genetic structure of three ethnic territorial groups from the north of European Russia (Continental Nentsy, Kola Saami, and Russian Coast-dwellers) was described. In general, the groups studied a Caucasoid pattern of the frequency distribution of erythrocytic marker alleles. However, a substantial contribution of a Mongoloid component to the Nenets gene pool, expressed as a high frequency of the PGM1*1 allele along with a low frequency of the GLO1*1 allele, was observed. Three ethnic territorial groups examined were close to one another with respect to the distribution of classical biochemical markers. The interpopulation diversity was low (the mean FST = 0.015). The differences observed were for the most part caused by the genetic characteristics of Nentsy. The maximum interpopulation diversity was observed for the GLO1 locus (FST = 0.056).

ABO Blood-Group System↗
PubMed2004

[Relationship between genetic polymorphism of NAT2 and susceptibility to urinary bladder cancer].

OBJECTIVE: To study the relationship between genetic polymorphism of NAT2 and susceptibility to bladder cancer. METHODS: NAT2 genotypes were determined by PCR-RFLP method in 69 patients with bladder transitional cell carcinoma and 88 healthy controls. RESULTS: The frequency of NAT2 slow genotypes was 26.1% (18/69) in patients compared with 14.8% (13/88) in controls (P < 0.05). Bladder cancer risk in patients with NAT2 slow genotypes was 2 fold as high as that in patients with NAT2 rapid genotypes. When NAT2 rapid genotypes/non-smoker were used as reference, bladder cancer risk increased to 5.8-fold (P < 0.05). Among the smokers with PY higher than 10, the patients showed a higher frequency of NAT2 slow genotype than controls (P < 0.05). It was also shown that the patients with slow NAT2 genotypes were more likely to have high grade tumor (P < 0.05) and advanced stage tumor (P < 0.01). CONCLUSION: The results suggest that NAT2 genetic polymorphism is associated with bladder cancer susceptibility. People with NAT2 slow genotype have higher bladder cancer risk.

Arylamine N-Acetyltransferase↗
PubMed1999

[Genetic polymorphisms of homocysteine metabolism related enzymes in patients with coronary heart disease].

OBJECTIVE: To study genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677T and cystathionine beta-synthase(CBS) T833C related to homocysteine metabolism in patients with coronary heart disease (CHD). METHODS: 209 patients with CHD and 101 controls were selected. MTHFR genetic C677T polymorphism was determined by PCR-RFLP, and CBS T833C polymorphism by ARMS method. Plasma homocysteine levels were detected with HPLC. RESULTS: The frequencies of MTHFR T homogenetic type and heterogenetic type (27.8% and 45.4%) in case group were higher than those in normal group(22.8% and 34.6%). There were significant differences in the frequencies of genotypes and alleles between two groups (P < 0.05). C homogenotype of CBS gene was found in 21 patients, and 2 in the normal group. There were evident differences in the frequencies of genotypes and alleles of the two groups (P < 0.001). Moreover, plama homocysteine levels were markedly higher in patients with MTHFR or CBS genetic mutation than those in patients without mutation (P < 0.05). CONCLUSIONS: Hyperhomocysteinemia is an independent risk factor of CHD. MTHFR and CBS are the main enzymes related to homocysteine metabolism. Their genetic mutations are possibly important mechanism of hyperhomocysteinemia and coronary heart disease.

Adult↗
PubMed2004

Genetic polymorphism of VEGF: Impact on longitudinal change of peritoneal transport and survival of peritoneal dialysis patients.

BACKGROUND: Vascular endothelial growth factor (VEGF) plays a pivotal role in the peritoneal angiogenesis and hyperpermeability in patients on peritoneal dialysis. We hypothesis that VEGF genetic polymorphism may affect the longitudinal change of peritoneal transport and clinical outcome of peritoneal dialysis patients. METHODS: We studied 135 consecutive new peritoneal dialysis patients. VEGF genetic polymorphism at -1154 and -2578 positions were determined by polymerase chain reaction (PCR) methodologies. Standard peritoneal test and dialysis adequacy and transport test (DATT) were performed at the initiation of peritoneal dialysis. After 12 months, DATT was repeated in 83 patients. In 35 patients, VEGF production in vivo was determined by its levels in serum and peritoneal dialysis effluent, and mRNA expression in peritoneal dialysis effluent. Patients were followed for 19.4 +/- 8.5 months for survival study. RESULTS: There was no relation between VEGF genotype and baseline peritoneal transport group. The changes in 24-hour dialysate-to-plasma (D/P) creatinine after 12 months were 0.028 +/- 0.159, -0.013 +/- 0.137, and 0.141 +/- 0.231 for CC, CA, and AA genotype at -2578 position, respectively [one-way analysis of variance (ANOVA), P= 0.028]. The AA genotype had significantly higher increase in 24-hour D/P creatinine than the other genotypes. Similar results were found with the genotype at -1154 position, which had marked linkage disequilibrium with the genotype at -2578 position. Actuarial patient survival was 90.3% and 74.9% at 24 months for CC and CA/AA genotypes at -2578 position, respectively (P= 0.036). After correcting for confounding covariates, the adjusted hazard ratio of death was 3.04 (95% CI, 1.10 to 8.36) for the CA/AA group as compared to CC group. Although baseline serum VEGF level was higher in patients with CC genotype than those with CA/AA genotype at -2578 position (541.5 +/- 322.8 pg/mL vs. 298.8 +/- 209.4 pg/mL, P= 0.012), VEGF mRNA expression in peritoneal dialysis effluent was significantly lower in patients with CC genotype (1.82 +/- 2.77 vs 4.48 +/- 3.28, P= 0.021). VEGF protein level in peritoneal dialysis effluent was also marginally lower in patients with CC genotype, although the difference was not significant. Genotype at -1154 position was not associated with VEGF production in vivo or patient survival. CONCLUSION: We conclude that in peritoneal dialysis patients, the AA genotype of VEGF promoter at -2578 position was associated with progressive increase in peritoneal transport. The CA/AA genotype at -2578 position was also associated with an excess mortality. Our finding also suggests that systemic and local peritoneal VEGF production may be differentially regulated.

Adult↗
PubMed1998

[Genetic polymorphism of drug metabolizing enzymes: new mutations in CYP2D6 and CYP2A6 genes in Japanese].

Interindividual variation of drug effects in humans can be attributed to many factors. Among the factors, the rate of drug metabolism has been regarded as the most important one. A genetic defect of enzymes involved in drug metabolism, particularly cytochrome P450 (CYP), has been believed to be one of the important causal factors of adverse drug reactions. There are multiple gene mutations for CYP causing the poor metabolizer phenotype. The occurrence of genetic polymorphism has been seen in genes for CYP1A1, CYP2A6, CYP2C9, CYP2D19, CYP2D6, CYP2E1 and CYP3A5. Among them, the molecular mechanisms of genetic polymorphisms of CYP2D6 (debrisoquine/sparteine type) and CYP2A6 (coumarin type) in Japanese have been the focus of investigations. Only 20-30% of the Japanese population that shows the CYP2D6 poor metabolizer phenotype can be diagnosed by gene analysis. By other means, we found two new mutations, CYP2D6/J9 and CYP2D6/C8, in Japanese. With regard to CYP2A6, we discovered SM-12502, a new probe drug in addition to coumarin, that is currently under development; this drug is mainly metabolized by CYP2A6. Using this drug as a probe, we found poor metabolizers and analyzed the genes for CYP2A6. We found a new mutation (CYP2A6 whole deletion) responsible for the poor metabolizer phenotype. These results should contribute to the selection of an effective drug prescription and a reduced incidence of adverse effects.

Alleles↗
PubMed1998

Glutathione S-transferase mu1 and N-acetyltransferase 2 genetic polymorphisms and exposure to tobacco smoke in nonsmoking and smoking lung cancer patients and population controls.

We conducted a case-control study to assess the risk of lung cancer in relation to genetic polymorphisms of the detoxifying enzymes glutathione-S-transferase mu1 (GSTM1) and N-acetyl transferase 2 (NAT2), focusing on never-smokers, women, and older people. The study base consisted of persons > or =30 years of age in Stockholm County from 1992 to 1995. We recruited never-smoking lung cancer cases and a sex- and age-matched sample of ever-smoking cases at the three county hospitals mainly responsible for diagnosing and treating lung cancer. A total of 185 cases (25.4% men; 47.6% never-smokers) and 164 frequency-matched population controls (28.7% men; 48.2% never-smokers) supplied blood for genotyping. Detailed information was collected by interview on active and passive smoking, occupations, residences, and diet. The overall odds ratio (OR) for lung cancer associated with the GSTM1 null (GSTM1-) versus GSTM1+ genotype was 0.8 [95% confidence interval (CI), 0.5-1.2], with an OR close to unity among smokers, and lower ORs suggested among never-smokers. For NAT2 slow versus rapid acetylator genotypes, the OR was 1.0 (95% CI, 0.6-1.5) overall, which broke down into an increased risk for slow acetylators among never-smokers but an increased risk for rapid acetylators among smokers. Among never-smokers, a gene interaction was suggested, with combined slow acetylator and GSTM1+ genotype conferring particularly high risk (OR = 3.1; 95% CI, 1.1-8.6), but no clear pattern emerged among smokers. A detailed analysis among smokers showed no interaction between pack-years of smoking and the GSTM1 genotype but suggested a steeper increase in risk with increasing pack-years of smoking exposure for rapid than for slow acetylators. Our results do not support a major role for the GSTM1 genetic polymorphism as a risk factor for lung cancer among smokers or nonsmokers. There was, however, some suggestion that the slow acetylator genotype may confer an increased risk among never-smokers and that the rapid acetylator genotype interacts with pack-year dose to produce a steeper risk gradient among smokers.

Acetylation↗
PubMed1988

Genetic polymorphism of natural Epstein-Barr virus isolates from infectious mononucleosis patients and healthy carriers.

We analyzed Epstein-Barr virus (EBV) genomes from lymphoblastoid cell lines isolated from patients with infectious mononucleosis and from healthy subjects from California, Hawaii, and Hong Kong between 1970 and 1987. Using genetic polymorphism as epidemiological markers, we found that several genotypes of EBV cocirculate in a community and that although most EBV strains isolated from California and Southern China may be differentiated genotypically, there was no specific association between genotype and disease or time of isolation.

B-Lymphocytes↗
PubMed2000

G-2964A and C734A genetic polymorphisms of CYP1A2 in Chinese population.

AIM: To observe the G-2964A and C734A genetic polymorphisms of human CYP1A2 in Chinese population. METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was employed in genotyping analysis. RESULTS: The allele frequencies of A-2964 were 0.25 and 0.22 in Qidong and Changsha populations, respectively. The incidences of A734 were 0.68 in Qidong population and 0.66 in Changsha population. No more than two low-inducibility/activity alleles were presented in one person. CONCLUSION: The distribution of the G-2964A and C734A genetic polymorphisms did not show significant difference between Chinese and Japanese populations. The incidence of C734A in Chinese was also similar to that in Caucasian population.

Adult↗
PubMed2000

Genetic polymorphisms of p53 and GSTP1,but not NAT2,are associated with susceptibility to squamous-cell carcinoma of the esophagus.

The interaction of genetic and environmental factors can determine an individual's susceptibility to various cancers. We present a hospital-based case-control study, which included 90 patients of esophageal squamous-cell carcinoma (ESCC) and 254 healthy people in Taiwan, to investigate the effects of genetic polymorphisms of p53, GSTP1 and NAT2 on the risk of ESCC. Polymorphisms of p53, NAT2 and GSTP1 were determined by PCR-RFLP. The codon 72 p53 Pro allele was more frequently found in ESCC patients [odds ratio (OR) 1.86, 95% confidence interval (CI) 1.04-3.35 for Arg/Pro genotype and OR 2.56, 95% CI 1.29-5.08 for Pro/Pro genotype]. In cigarette smokers, the frequency of GSTP1 Ile/Ile genotype was higher in ESCC patients (OR 2.8, 95% CI 1.4-5.7). Among alcohol drinkers, borderline significance was also found for GSTP1 Ile/Ile genotype (OR 2.0, 95% CI 0.9-4.4). Results were not similar for the NAT2 genetic polymorphism. Using logistic analyses, we found that individuals with p53 Pro/Pro genotype had a significantly higher risk of developing ESCC than those with Arg/Arg genotype (OR 2.3, 95% CI 1. 1-5.1), after adjusting for other significant environmental risk factors. This result remained similar (OR 2.2, 95% CI 1.0-4.8 for p53 Pro/Pro vs. Arg/Arg), even after further adjustment for NAT2 and GSTP1 polymorphisms. The codon 72 p53 Pro/Pro genotype in the general population and GSTP1 Ile/Ile in cigarette smokers may predict a higher risk of developing ESCC.

Adult↗
PubMed2003

Genetic polymorphisms and modulation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-DNA adducts in human lymphocytes.

2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant heterocyclic amine derived from food, possibly involved in human carcinogenesis. We evaluated the formation of PhIP-DNA adducts in lymphocytes from 76 incident colorectal cancer patients likely to be exposed to dietary PhIP. To address the role of the metabolic polymorphisms relevant to PhIP-DNA adduct formation, the patients were genotyped for common polymorphisms in the N-acetyltransferase (NAT1 and NAT2), sulfotransferase (SULT1A1) and glutathione S-transferase (GSTM1 and GSTA1) genes. PhIP released from adducted DNA after hydrolysis was quantitated by liquid chromatography-tandem mass spectrometry. Overall, adducts were 3.24 +/- 3.58/10(8) nucleotides (mean +/- SD); they were not related to sex, smoking habits or age, though levels were not significantly higher in smokers, young subjects and high meat consumers. High vegetable intake significantly reduced PhIP-DNA adducts (Mann-Whitney U, p = 0.044). Individuals with the GSTM1 null genotype showed colon cancer onset at earlier age (58.8 +/- 1.8 vs. 63.5 +/- 1.6 years; Mann-Whitney U, p = 0.047). None of the genetic polymorphisms studied significantly affected PhIP-DNA adducts. However, individuals carrying 2 mutated GSTA1 alleles and younger than the median age had higher adduct levels than homozygous wild-type and heterozygous ones (Kruskal-Wallis p = 0.0008). In conclusion, these preliminary data indicate that PhIP-DNA adducts are formed in people likely to be exposed to this carcinogen through the diet, suggesting this biomarker may be useful to detect human exposure and DNA damage. Overall, the genetic polymorphisms considered had limited effect on PhIP-DNA levels, but young people with lower detoxification capacity may form a subgroup particularly susceptible to dietary carcinogen.

Colorectal Neoplasms↗
PubMed2001

Lack of association among five genetic polymorphisms of the renin-angiotensin system and cardiac hypertrophy in patients with aortic stenosis.

BACKGROUND: Patients with aortic stenosis (AS) have left ventricular hypertrophy (LVH). It is thought that LVH in these patients is a consequence of chronic left ventricular pressure overload. However, there is only a poor correlation between the degree of AS and the degree of LVH. Genetic polymorphisms of the renin-angiotensin-aldosterone system (RAAS) have been considered to trigger the response of the left ventricle to chronic pressure overload and determine the degree of LVH in patients with AS. METHODS: One hundred five consecutive patients with symptomatic AS were examined by echocardiography and left heart catheterization to determine the severity of AS and LVH. Five genetic polymorphisms of the RAAS (ACE, AGTR1, AGT, CMA, CYP11B2) were analyzed in all patients and the results of genetic analysis were correlated to severity of AS and LVH to determine the importance of the polymorphisms for LVH. RESULTS: All tested genotypes were in Hardy-Weinberg equilibrium and allele frequencies were similar to other study populations. There was no correlation between the severity of AS and the severity of LVH. There was no association between the five tested genotypes of the RAAS and the severity of AS (mean gradient and area of the aortic valve) or LVH (LV muscle mass). CONCLUSION: We conclude that LVH in patients with AS is not determined by the tested genetic polymorphisms of the RAAS.

Aged↗