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Ulrich H. Frey - One of the best experts on this subject based on the ideXlab platform.

  • GNB3 gene 825 tt variant predicts hard coronary events in the population based heinz nixdorf recall study
    Atherosclerosis, 2014
    Co-Authors: Ulrich H. Frey, Susanne Moebus, Stefan Mohlenkamp, Hagen Kalsch, Marcus Bauer, Nils Lehmann, Markus M Nothen, Thomas W Muhleisen, Andreas Stang
    Abstract:

    Abstract Objective The C825T polymorphism of the gene encoding the human G protein beta-3 subunit ( GNB3 ) is associated with hypertension and obesity. Moreover, genotypes of the GNB3 polymorphism have been associated with development of coronary artery disease, and the 825T allele is thought to influence the process of atherosclerosis. However, the potential of the C825T polymorphism to predict coronary events has been poorly explored in a longitudinal setting at the population level. Methods In 4159 Caucasian subjects from the Heinz Nixdorf Recall study cohort (age: 45–75 years, 48% male), genotypes of the GNB3 C825T polymorphism (rs5443) were determined and associated with fatal and non-fatal myocardial infarction (hard coronary events). Established cardiovascular risk factors were used to adjust for confounders. Results The median follow-up time was 9.9 years (1st/3rd quartiles 9.5/10.2). 148 subjects (3.6%) experienced a hard coronary event. The 10-year event-free survival rate was CC, 96.1%; CT 96.9%, TT, 93.7% ( p  = 0.018). Multivariable analysis showed that the TT genotype is a significant risk factor for hard coronary events (hazard ratio (HR) = 1.9 (95% confidence interval (CI) 1.2–2.9); p  = 0.008) after adjustment for age, sex, diabetes, systolic blood pressure, body mass index, high-density lipoprotein, and coronary artery calcification as determined by electron beam computed tomography at baseline. While prognosis in females was independent of GNB3 genotypes, analysis in males even elevated the HR for TT versus C-allele to 2.6 (95% CI 1.6–4.2; p Conclusion The GNB3 825 TT genotype is a significant and independent risk factor for hard coronary events independent of other established cardiovascular risk factors at a population level in males.

  • GNB3 gene 825 TT variant predicts hard coronary events in the population-based Heinz Nixdorf Recall study.
    Atherosclerosis, 2014
    Co-Authors: Ulrich H. Frey, Susanne Moebus, Stefan Mohlenkamp, Hagen Kalsch, Marcus Bauer, Nils Lehmann, Markus M Nothen, Thomas W Muhleisen, Andreas Stang, Raimund Erbel
    Abstract:

    The C825T polymorphism of the gene encoding the human G protein beta-3 subunit (GNB3) is associated with hypertension and obesity. Moreover, genotypes of the GNB3 polymorphism have been associated with development of coronary artery disease, and the 825T allele is thought to influence the process of atherosclerosis. However, the potential of the C825T polymorphism to predict coronary events has been poorly explored in a longitudinal setting at the population level. In 4159 Caucasian subjects from the Heinz Nixdorf Recall study cohort (age: 45-75 years, 48% male), genotypes of the GNB3 C825T polymorphism (rs5443) were determined and associated with fatal and non-fatal myocardial infarction (hard coronary events). Established cardiovascular risk factors were used to adjust for confounders. The median follow-up time was 9.9 years (1st/3rd quartiles 9.5/10.2). 148 subjects (3.6%) experienced a hard coronary event. The 10-year event-free survival rate was CC, 96.1%; CT 96.9%, TT, 93.7% (p = 0.018). Multivariable analysis showed that the TT genotype is a significant risk factor for hard coronary events (hazard ratio (HR) = 1.9 (95% confidence interval (CI) 1.2-2.9); p = 0.008) after adjustment for age, sex, diabetes, systolic blood pressure, body mass index, high-density lipoprotein, and coronary artery calcification as determined by electron beam computed tomography at baseline. While prognosis in females was independent of GNB3 genotypes, analysis in males even elevated the HR for TT versus C-allele to 2.6 (95% CI 1.6-4.2; p < 0.001). The GNB3 825 TT genotype is a significant and independent risk factor for hard coronary events independent of other established cardiovascular risk factors at a population level in males. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  • Association of the GNB3 825T-allele with better survival in patients with glioblastoma multiforme.
    Journal of cancer research and clinical oncology, 2010
    Co-Authors: Nicolai El Hindy, Ulrich H. Frey, Michael Adamzik, Nicole Lambertz, Hagen S. Bachmann, Karl Worm, Rupert Egensperger, Siamak Asgari, Ulrich Sure, Winfried Siffert
    Abstract:

    Purpose Genotypes of the C825T polymorphism of the GNB3 gene encoding the G protein β3 subunit were recently associated with the prognosis of different malignomas. We investigated potential associations of GNB3 genotypes with survival of patients with glioblastoma multiforme (GBM).

  • Hunger and mood during extended fasting are dependent on the GNB3 C825T polymorphism.
    Annals of nutrition & metabolism, 2009
    Co-Authors: Andreas Michalsen, Ulrich H. Frey, Winfried Siffert, Stefanie Merse, Gustav Dobos
    Abstract:

    The 825T allele of the G protein beta3-subunit gene (GNB3) is a thrifty genotype associated with an increased risk for obesity. We aimed to determine whether the 825T allele is modifying the subjective response to extended fasting. We genotyped 108 subjects who underwent an 8-day modified medical fasting treatment [total energy intake <350 kcal (1465 kJ)/day] for the GNB3 C825T polymorphism. Perceived hunger and mood were recorded daily by self-rating visual analogue scales. Whereas weight loss was not dependent on genotype, both mood and hunger were significantly associated with genotype, with homozygous CC genotype carriers having best mood (p = 0.004) and least hunger (p = 0.036) during fasting compared to TT genotype carriers. Pronounced mental discomfort during fasting in 825T allele carriers might partly explain their increased risk for obesity. The strong association between the subjective response to fasting with GNB3 genotypes indicates a role of the gene in the behavioural regulation of food intake, which should be further considered in nutritional intervention studies. 2009 S. Karger AG, Basel.

  • GNB3 c825t polymorphism and response to interferon alfa ribavirin treatment in patients with hepatitis c virus genotype 1 hcv 1 infection
    Journal of Hepatology, 2005
    Co-Authors: Christoph Sarrazin, T Berg, V. Weich, Tobias Mueller, Ulrich H. Frey, Stefan Zeuzem, Guido Gerken, Michael Roggendorf, Winfried Siffert
    Abstract:

    Background/Aims The outcome of infection with the hepatitis C virus (HCV) has been shown to be influenced by genetic host factors. The G protein β3 subunit ( GNB3 ) C825T polymorphism has been shown to determine immune cell functions in vitro. We investigated the association of GNB3 genotypes with treatment response in HCV-infected patients. Methods We genotyped 1781 HCV-free blood donors and 232 HCV-infected patients treated with interferon-alfa/ribavirin. Sustained virologic response (SVR) was defined by undetectable HCV-RNA 24 weeks after discontinuation of therapy. Non-response (NR) was defined by positive HCV-RNA at the end of at least 24 weeks of treatment. GNB3 genotypes were determined by DNA restriction enzyme analyses. Results Genotype distribution was not significantly different in healthy controls and HCV-infected patients. Only in HCV genotype 1-infected patients a significant correlation between GNB3 CC genotype and NR could be observed (6 TT, 42 TC, 54 CC) versus SVR (11 TT, 25 TC, 19 CC) patients ( P =0.004). In a logistic regression analysis including biochemical and virologic characteristics, only GNB3 CC genotype was significantly associated with NR (OR 4.9; 95% CI=1.4–16.5; P =0.011). Conclusions The GNB3 825 CC genotype is associated with NR in HCV-1-infected patients.

Winfried Siffert - One of the best experts on this subject based on the ideXlab platform.

  • Association of the GNB3 825T-allele with better survival in patients with glioblastoma multiforme.
    Journal of cancer research and clinical oncology, 2010
    Co-Authors: Nicolai El Hindy, Ulrich H. Frey, Michael Adamzik, Nicole Lambertz, Hagen S. Bachmann, Karl Worm, Rupert Egensperger, Siamak Asgari, Ulrich Sure, Winfried Siffert
    Abstract:

    Purpose Genotypes of the C825T polymorphism of the GNB3 gene encoding the G protein β3 subunit were recently associated with the prognosis of different malignomas. We investigated potential associations of GNB3 genotypes with survival of patients with glioblastoma multiforme (GBM).

  • Hunger and mood during extended fasting are dependent on the GNB3 C825T polymorphism.
    Annals of nutrition & metabolism, 2009
    Co-Authors: Andreas Michalsen, Ulrich H. Frey, Winfried Siffert, Stefanie Merse, Gustav Dobos
    Abstract:

    The 825T allele of the G protein beta3-subunit gene (GNB3) is a thrifty genotype associated with an increased risk for obesity. We aimed to determine whether the 825T allele is modifying the subjective response to extended fasting. We genotyped 108 subjects who underwent an 8-day modified medical fasting treatment [total energy intake <350 kcal (1465 kJ)/day] for the GNB3 C825T polymorphism. Perceived hunger and mood were recorded daily by self-rating visual analogue scales. Whereas weight loss was not dependent on genotype, both mood and hunger were significantly associated with genotype, with homozygous CC genotype carriers having best mood (p = 0.004) and least hunger (p = 0.036) during fasting compared to TT genotype carriers. Pronounced mental discomfort during fasting in 825T allele carriers might partly explain their increased risk for obesity. The strong association between the subjective response to fasting with GNB3 genotypes indicates a role of the gene in the behavioural regulation of food intake, which should be further considered in nutritional intervention studies. 2009 S. Karger AG, Basel.

  • GNB3 c825t polymorphism and response to interferon alfa ribavirin treatment in patients with hepatitis c virus genotype 1 hcv 1 infection
    Journal of Hepatology, 2005
    Co-Authors: Christoph Sarrazin, T Berg, V. Weich, Tobias Mueller, Ulrich H. Frey, Stefan Zeuzem, Guido Gerken, Michael Roggendorf, Winfried Siffert
    Abstract:

    Background/Aims The outcome of infection with the hepatitis C virus (HCV) has been shown to be influenced by genetic host factors. The G protein β3 subunit ( GNB3 ) C825T polymorphism has been shown to determine immune cell functions in vitro. We investigated the association of GNB3 genotypes with treatment response in HCV-infected patients. Methods We genotyped 1781 HCV-free blood donors and 232 HCV-infected patients treated with interferon-alfa/ribavirin. Sustained virologic response (SVR) was defined by undetectable HCV-RNA 24 weeks after discontinuation of therapy. Non-response (NR) was defined by positive HCV-RNA at the end of at least 24 weeks of treatment. GNB3 genotypes were determined by DNA restriction enzyme analyses. Results Genotype distribution was not significantly different in healthy controls and HCV-infected patients. Only in HCV genotype 1-infected patients a significant correlation between GNB3 CC genotype and NR could be observed (6 TT, 42 TC, 54 CC) versus SVR (11 TT, 25 TC, 19 CC) patients ( P =0.004). In a logistic regression analysis including biochemical and virologic characteristics, only GNB3 CC genotype was significantly associated with NR (OR 4.9; 95% CI=1.4–16.5; P =0.011). Conclusions The GNB3 825 CC genotype is associated with NR in HCV-1-infected patients.

  • GNB3 C825T polymorphism and response to interferon-alfa/ribavirin treatment in patients with hepatitis C virus genotype 1 (HCV-1) infection.
    Journal of hepatology, 2005
    Co-Authors: Christoph Sarrazin, T Berg, V. Weich, Tobias Mueller, Ulrich H. Frey, Stefan Zeuzem, Guido Gerken, Michael Roggendorf, Winfried Siffert
    Abstract:

    The outcome of infection with the hepatitis C virus (HCV) has been shown to be influenced by genetic host factors. The G protein beta3 subunit (GNB3) C825T polymorphism has been shown to determine immune cell functions in vitro. We investigated the association of GNB3 genotypes with treatment response in HCV-infected patients. We genotyped 1781 HCV-free blood donors and 232 HCV-infected patients treated with interferon-alfa/ribavirin. Sustained virologic response (SVR) was defined by undetectable HCV-RNA 24 weeks after discontinuation of therapy. Non-response (NR) was defined by positive HCV-RNA at the end of at least 24 weeks of treatment. GNB3 genotypes were determined by DNA restriction enzyme analyses. Genotype distribution was not significantly different in healthy controls and HCV-infected patients. Only in HCV genotype 1-infected patients a significant correlation between GNB3 CC genotype and NR could be observed (6 TT, 42 TC, 54 CC) versus SVR (11 TT, 25 TC, 19 CC) patients (P = 0.004). In a logistic regression analysis including biochemical and virologic characteristics, only GNB3 CC genotype was significantly associated with NR (OR 4.9; 95% CI = 1.4-16.5; P = 0.011). The GNB3 825 CC genotype is associated with NR in HCV-1-infected patients.

  • The CC Genotype of the C825T Polymorphism of the G Protein β3 Gene (GNB3) is Associated with a High Relapse Rate in Patients with Chronic Lymphocytic Leukaemia
    Leukemia & lymphoma, 2003
    Co-Authors: Holger Nückel, Ulrich H. Frey, Nese Aral, Jan Dürig, Ulrich Dührsen, Winfried Siffert
    Abstract:

    A C825T polymorphism has been described in the GNB3 gene which encodes the Gbeta3 subunit of heterotrimeric G proteins.The GNB3 825T allele is predictive of enhanced Gi protein activation. This study was performed to correlate genotypes of the C825T polymorphism with various clinical aspects of chronic lymphocytic leukaemia (B-CLL). The GNB3 genotype distribution in B-CLL patients was similar to that in other Caucasian populations, arguing against a role of the polymorphism in the susceptibility to develop B-CLL. No statistically significant differences were observed at diagnosis between patients with the CC genotype and homozygous or heterozygous T allele carriers with respect to age at disease onset, sex distribution, proportion of patients with CD38+ leukaemia or patients in Binet stage A, blood cell counts, degree of bone marrow infiltration or serum levels of lactate dehydrogenase, thymidine kinase or β2-microglobulin. In a subgroup of 44 patients requiring chemotherapy, the median interval between d...

Andreas Stang - One of the best experts on this subject based on the ideXlab platform.

  • GNB3 gene 825 tt variant predicts hard coronary events in the population based heinz nixdorf recall study
    Atherosclerosis, 2014
    Co-Authors: Ulrich H. Frey, Susanne Moebus, Stefan Mohlenkamp, Hagen Kalsch, Marcus Bauer, Nils Lehmann, Markus M Nothen, Thomas W Muhleisen, Andreas Stang
    Abstract:

    Abstract Objective The C825T polymorphism of the gene encoding the human G protein beta-3 subunit ( GNB3 ) is associated with hypertension and obesity. Moreover, genotypes of the GNB3 polymorphism have been associated with development of coronary artery disease, and the 825T allele is thought to influence the process of atherosclerosis. However, the potential of the C825T polymorphism to predict coronary events has been poorly explored in a longitudinal setting at the population level. Methods In 4159 Caucasian subjects from the Heinz Nixdorf Recall study cohort (age: 45–75 years, 48% male), genotypes of the GNB3 C825T polymorphism (rs5443) were determined and associated with fatal and non-fatal myocardial infarction (hard coronary events). Established cardiovascular risk factors were used to adjust for confounders. Results The median follow-up time was 9.9 years (1st/3rd quartiles 9.5/10.2). 148 subjects (3.6%) experienced a hard coronary event. The 10-year event-free survival rate was CC, 96.1%; CT 96.9%, TT, 93.7% ( p  = 0.018). Multivariable analysis showed that the TT genotype is a significant risk factor for hard coronary events (hazard ratio (HR) = 1.9 (95% confidence interval (CI) 1.2–2.9); p  = 0.008) after adjustment for age, sex, diabetes, systolic blood pressure, body mass index, high-density lipoprotein, and coronary artery calcification as determined by electron beam computed tomography at baseline. While prognosis in females was independent of GNB3 genotypes, analysis in males even elevated the HR for TT versus C-allele to 2.6 (95% CI 1.6–4.2; p Conclusion The GNB3 825 TT genotype is a significant and independent risk factor for hard coronary events independent of other established cardiovascular risk factors at a population level in males.

  • GNB3 gene 825 TT variant predicts hard coronary events in the population-based Heinz Nixdorf Recall study.
    Atherosclerosis, 2014
    Co-Authors: Ulrich H. Frey, Susanne Moebus, Stefan Mohlenkamp, Hagen Kalsch, Marcus Bauer, Nils Lehmann, Markus M Nothen, Thomas W Muhleisen, Andreas Stang, Raimund Erbel
    Abstract:

    The C825T polymorphism of the gene encoding the human G protein beta-3 subunit (GNB3) is associated with hypertension and obesity. Moreover, genotypes of the GNB3 polymorphism have been associated with development of coronary artery disease, and the 825T allele is thought to influence the process of atherosclerosis. However, the potential of the C825T polymorphism to predict coronary events has been poorly explored in a longitudinal setting at the population level. In 4159 Caucasian subjects from the Heinz Nixdorf Recall study cohort (age: 45-75 years, 48% male), genotypes of the GNB3 C825T polymorphism (rs5443) were determined and associated with fatal and non-fatal myocardial infarction (hard coronary events). Established cardiovascular risk factors were used to adjust for confounders. The median follow-up time was 9.9 years (1st/3rd quartiles 9.5/10.2). 148 subjects (3.6%) experienced a hard coronary event. The 10-year event-free survival rate was CC, 96.1%; CT 96.9%, TT, 93.7% (p = 0.018). Multivariable analysis showed that the TT genotype is a significant risk factor for hard coronary events (hazard ratio (HR) = 1.9 (95% confidence interval (CI) 1.2-2.9); p = 0.008) after adjustment for age, sex, diabetes, systolic blood pressure, body mass index, high-density lipoprotein, and coronary artery calcification as determined by electron beam computed tomography at baseline. While prognosis in females was independent of GNB3 genotypes, analysis in males even elevated the HR for TT versus C-allele to 2.6 (95% CI 1.6-4.2; p < 0.001). The GNB3 825 TT genotype is a significant and independent risk factor for hard coronary events independent of other established cardiovascular risk factors at a population level in males. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Eugene Lin - One of the best experts on this subject based on the ideXlab platform.

  • association of the c825t polymorphism in the GNB3 gene with obesity and metabolic phenotypes in a taiwanese population
    Genes and Nutrition, 2013
    Co-Authors: Tunjen Hsiao, Yuchi Hwang, Canhong Liu, Huamei Chang, Eugene Lin
    Abstract:

    The relationship between obesity and a single nucleotide polymorphism (SNP), rs5443 (C825T), in the guanine nucleotide binding protein beta polypeptide 3 (GNB3) gene is currently inconsistent. In this study, we aimed to reassess whether the GNB3 rs5443 SNP could influence obesity and obesity-related metabolic traits in a Taiwanese population. A total of 983 Taiwanese subjects with general health examinations were genotyped. Based on the criteria defined by the Department of Health in Taiwan, the terms “overweight” and “obesity” are defined as 24 ≦ BMI < 27 and BMI ≧ 27, respectively. Compared to the carrier of the combined CT + TT genotypes of the GNB3 rs5443 polymorphism, triglyceride was significantly higher for the carrier of CC genotype in the complete sample population (128.2 ± 93.2 vs. 114.3 ± 79.1 mg/dl; P = 0.041). In addition, the carriers of CC variant had a higher total cholesterol than those with the combined CT + TT variants (194.5 ± 36.8 vs. 187.9 ± 33.0 mg/dl; P = 0.019) in the complete sample population. In the normal controls, both triglyceride (P = 0.018) and total cholesterol (P = 0.011) were also significantly higher in the CC homozygotes than in the combined CT + TT genotypes. However, the GNB3 rs5443 SNP did not exhibit any significant association with obesity or overweight among the subjects. Our study indicates that the CC genotype of the GNB3 rs5443 SNP may predict higher obesity-related metabolic traits such as triglyceride and total cholesterol in non-obese Taiwanese subjects (but not in obese subjects).

  • Association of the C825T polymorphism in the GNB3 gene with obesity and metabolic phenotypes in a Taiwanese population
    Genes & nutrition, 2012
    Co-Authors: Tunjen Hsiao, Yuchi Hwang, Canhong Liu, Huamei Chang, Eugene Lin
    Abstract:

    The relationship between obesity and a single nucleotide polymorphism (SNP), rs5443 (C825T), in the guanine nucleotide binding protein beta polypeptide 3 (GNB3) gene is currently inconsistent. In this study, we aimed to reassess whether the GNB3 rs5443 SNP could influence obesity and obesity-related metabolic traits in a Taiwanese population. A total of 983 Taiwanese subjects with general health examinations were genotyped. Based on the criteria defined by the Department of Health in Taiwan, the terms "overweight" and "obesity" are defined as 24 ≦ BMI 

  • Weight loss and body fat reduction under sibutramine therapy in obesity with the C825T polymorphism in the GNB3 gene.
    Pharmacogenetics and genomics, 2009
    Co-Authors: Dun Jen Hsiao, Shih Yi Huang, Eugene Lin
    Abstract:

    The relationship between weight reduction after sibutramine treatment and a single nucleotide polymorphism, rs5443 (C825T), in the guanine nucleotide binding protein beta polypeptide 3 (GNB3) gene is currently inconsistent. In this study, we aimed to reassess whether the GNB3 rs5443 single nucleotide polymorphism could influence weight reduction and body composition change under sibutramine therapy in 131 obese Taiwanese patients. By comparing the sibutramine and placebo groups with analysis of covariance, our data showed a strong effect of sibutramine on weight reduction (7.4+/-1.4 vs. 3.4+/-1.2 kg; P

Raimund Erbel - One of the best experts on this subject based on the ideXlab platform.

  • GNB3 gene 825 TT variant predicts hard coronary events in the population-based Heinz Nixdorf Recall study.
    Atherosclerosis, 2014
    Co-Authors: Ulrich H. Frey, Susanne Moebus, Stefan Mohlenkamp, Hagen Kalsch, Marcus Bauer, Nils Lehmann, Markus M Nothen, Thomas W Muhleisen, Andreas Stang, Raimund Erbel
    Abstract:

    The C825T polymorphism of the gene encoding the human G protein beta-3 subunit (GNB3) is associated with hypertension and obesity. Moreover, genotypes of the GNB3 polymorphism have been associated with development of coronary artery disease, and the 825T allele is thought to influence the process of atherosclerosis. However, the potential of the C825T polymorphism to predict coronary events has been poorly explored in a longitudinal setting at the population level. In 4159 Caucasian subjects from the Heinz Nixdorf Recall study cohort (age: 45-75 years, 48% male), genotypes of the GNB3 C825T polymorphism (rs5443) were determined and associated with fatal and non-fatal myocardial infarction (hard coronary events). Established cardiovascular risk factors were used to adjust for confounders. The median follow-up time was 9.9 years (1st/3rd quartiles 9.5/10.2). 148 subjects (3.6%) experienced a hard coronary event. The 10-year event-free survival rate was CC, 96.1%; CT 96.9%, TT, 93.7% (p = 0.018). Multivariable analysis showed that the TT genotype is a significant risk factor for hard coronary events (hazard ratio (HR) = 1.9 (95% confidence interval (CI) 1.2-2.9); p = 0.008) after adjustment for age, sex, diabetes, systolic blood pressure, body mass index, high-density lipoprotein, and coronary artery calcification as determined by electron beam computed tomography at baseline. While prognosis in females was independent of GNB3 genotypes, analysis in males even elevated the HR for TT versus C-allele to 2.6 (95% CI 1.6-4.2; p < 0.001). The GNB3 825 TT genotype is a significant and independent risk factor for hard coronary events independent of other established cardiovascular risk factors at a population level in males. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  • interaction of the ace d allele and the GNB3 825t allele in myocardial infarction
    Hypertension, 2000
    Co-Authors: Christoph Naber, Ulrich Wolfhard, Raimund Erbel, Johannes Husing, Winfried Siffert
    Abstract:

    Abstract —In polygenetic disorders, such as ischemic heart disease, the investigation of gene-gene interactions rather than determination of single gene effects is crucial to better understand the contribution of genetic factors. The 825T allele of the G-protein β3-subunit gene ( GNB3 ) associated with enhanced G-protein signaling is a candidate to interact with the angiotensin-converting enzyme ( ACE ) deletion/insertion (D/I) polymorphism to increase the risk for myocardial infarction (MI). The ACE D/I variant affects the renin-angiotensin system hormones that activate G-protein–coupled receptors. Genotyping at the ACE and GNB3 loci was performed on 585 patients with coronary artery disease with (n=270) or without (n=315) previous MI. Logistic regression analysis demonstrated a significant interaction between the ACE D allele and the GNB3 825T allele ( P <0.001). The odds ratio for MI, associated with the 825T allele, was not increased in the presence of the ACE II genotype (OR 0.5; P =0.09) but was significantly higher in 825T allele carriers with the ACE DI genotype (OR 1.9; P =0.01) and further increased in individuals with the ACE DD genotype (OR 2.4; P =0.02). The highest odds ratio was found in homozygous 825T allele carriers with the ACE DD genotype (OR 7.5; P =0.006). Our data suggest a significant interaction of the GNB3 825T allele with the ACE D allele in MI. These hypothesis-generating data may justify larger prospective studies.

  • Interaction of the ACE D allele and the GNB3 825T allele in myocardial infarction
    Hypertension (Dallas Tex. : 1979), 2000
    Co-Authors: Christoph Naber, Johannes Hüsing, Ulrich Wolfhard, Raimund Erbel, Winfried Siffert
    Abstract:

    Abstract —In polygenetic disorders, such as ischemic heart disease, the investigation of gene-gene interactions rather than determination of single gene effects is crucial to better understand the contribution of genetic factors. The 825T allele of the G-protein β3-subunit gene ( GNB3 ) associated with enhanced G-protein signaling is a candidate to interact with the angiotensin-converting enzyme ( ACE ) deletion/insertion (D/I) polymorphism to increase the risk for myocardial infarction (MI). The ACE D/I variant affects the renin-angiotensin system hormones that activate G-protein–coupled receptors. Genotyping at the ACE and GNB3 loci was performed on 585 patients with coronary artery disease with (n=270) or without (n=315) previous MI. Logistic regression analysis demonstrated a significant interaction between the ACE D allele and the GNB3 825T allele ( P