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Article: Angiotensin I-converting enzyme: genotype and disease associations.

Crisan, D / Carr, J

The Journal of molecular diagnostics : JMD

2001 Volume 2, Issue 3, Page(s) 105–115

MeSH term(s)	Cardiovascular Diseases/enzymology ; Cardiovascular Diseases/genetics ; Cardiovascular Diseases/metabolism ; Genotype ; Humans ; Kidney Diseases/enzymology ; Kidney Diseases/genetics ; Kidney Diseases/metabolism ; Peptidyl-Dipeptidase A/genetics ; Peptidyl-Dipeptidase A/metabolism ; Polymorphism, Genetic ; Renin-Angiotensin System/genetics ; Renin-Angiotensin System/physiology
Chemical Substances	Peptidyl-Dipeptidase A (EC 3.4.15.1)
Language	English
Publishing date	2001-01-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2000060-1
ISSN	1943-7811 ; 1525-1578
ISSN (online)	1943-7811
ISSN	1525-1578
DOI	10.1016/S1525-1578(10)60624-1
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Article: Correlation between angiotensin-converting-enzyme 2 gene polymorphisms and systemic sclerosis.

Miziołek, Bartosz / Kruszniewska-Rajs, Celina / Gola, Joanna / Bultrowicz, Monika / Miszczyk, Justyna / Pieczyrak, Robert / Frątczak, Aleksandra / Polak, Karina / Kucharz, Eugeniusz J / Bergler-Czop, Beata

Clinical and experimental rheumatology

2023 Volume 41, Issue 8, Page(s) 1652–1658

Abstract: ... of the gene coding of angiotensin-converting-enzyme 2 (ACE2) may account for its development. Three ... Objectives: Systemic sclerosis (SSc) is a disease with cardiovascular impairment and polymorphisms ... polymorphism. They had lower risk for development of any CVS disease (RR=0.4, p=0.051) and tendency to less ...

Abstract	Objectives: Systemic sclerosis (SSc) is a disease with cardiovascular impairment and polymorphisms of the gene coding of angiotensin-converting-enzyme 2 (ACE2) may account for its development. Three single nucleotide polymorphisms of ACE2 (C>G rs879922, G>A rs2285666 and A>G rs1978124) were found to increase the risk for development of arterial hypertension (AH) and cardiovascular (CVS) diseases in different ethnicities. We investigated associations of polymorphisms rs879922, rs2285666 and rs1978124 with the development of SSc. Methods: Genomic DNA was isolated from whole blood. Restriction-fragment-length polymorphism was used for genotyping of rs1978124, while detection of rs879922 and rs2285666 was based on TaqMan SNP Genotyping Assay. Serum level of ACE2 was assayed with commercially available ELISA test. Results: 81 SSc patients (60 women, 21 men) were enrolled. Allele C of rs879922 polymorphism was associated with significantly greater risk for development of AH (OR=2.5, p=0.018), but less frequent joint involvement. A strong tendency to earlier onset of Raynaud's phenomenon and SSc was seen in carriers of allele A of rs2285666 polymorphism. They had lower risk for development of any CVS disease (RR=0.4, p=0.051) and tendency to less frequent gastrointestinal involvement. Women with genotype AG of rs1978124 polymorphism had significantly more frequent digital tip ulcers and lower serum level of ACE2. Conclusions: Polymorphisms of ACE2 may account for the development of AH and CVS disorders in SSc patients. Strong tendencies to more frequent occurrence of disease specific characteristics distinct to macrovascular involvement will require further studies evaluating significance of ACE2 polymorphisms in SSc.
MeSH term(s)	Female ; Humans ; Male ; Angiotensin-Converting Enzyme 2/genetics ; Angiotensins/genetics ; Cardiovascular Diseases ; Hypertension ; Polymorphism, Single Nucleotide ; Scleroderma, Systemic/diagnosis ; Scleroderma, Systemic/genetics
Chemical Substances	Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Angiotensins ; ACE2 protein, human (EC 3.4.17.23)
Language	English
Publishing date	2023-07-04
Publishing country	Italy
Document type	Journal Article
ZDB-ID	605886-3
ISSN	1593-098X ; 0392-856X
ISSN (online)	1593-098X
ISSN	0392-856X
DOI	10.55563/clinexprheumatol/utmjnq
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Article ; Online: Genetic polymorphisms in the angiotensin converting enzyme, actinin 3 and paraoxonase 1 genes in women with diabetes and hypertension.

Arejano, Gabrielle Gaspar / Hoffmann, Laura Vargas / Ferreira Wyse, Linoska / Espíndola Correia, Poliana / Pieniz, Simone / Torma Botelho, Fabiana / Schneider, Augusto / Schadock, Ines / Castilho Barros, Carlos

Archives of endocrinology and metabolism

2023 Volume 68, Page(s) e210204

Abstract: Objective: To study associations between polymorphisms in the angiotensin converting enzyme (ACE ... about food consumption, physical activity level and socioeconomic status were applied.: Results: The XX genotype ... Additionally, high triglycerides and LDL levels were observed in carriers of the TT genotype of PON1, and lower ...

Abstract	Objective: To study associations between polymorphisms in the angiotensin converting enzyme (ACE I/D), actinin 3 (ACTN3 R577X) and paraoxonase 1 (PON1 T(-107)C) genes and chronic diseases (diabetes and hypertension) in women. Materials and methods: Genomic DNA was extracted from saliva samples of 78 women between 18 and 59 years old used for genetic polymorphism screening. Biochemical data were collected from the medical records in Basic Health Units from Southern Brazil. Questionnaires about food consumption, physical activity level and socioeconomic status were applied. Results: The XX genotype of ACTN3 was associated with low HDL levels and high triglycerides, total cholesterol and glucose levels. Additionally, high triglycerides and LDL levels were observed in carriers of the TT genotype of PON1, and lower total cholesterol levels were associated to the CC genotype. As expected, women with diabetes/hypertense had increased body weight, BMI (p = 0.02), waist circumference (p = 0.01), body fat percentage, blood pressure (p = 0.02), cholesterol, triglycerides (p = 0.02), and blood glucose (p = 0.01), when compared to the control group. Conclusion: Both ACTN3 R577X and PON1 T(-107)C polymorphisms are associated with nutritional status and blood glucose and lipid levels in women with diabetes/hypertense. These results contribute to genetic knowledge about predisposition to obesity-related diseases.
MeSH term(s)	Adolescent ; Adult ; Female ; Humans ; Middle Aged ; Young Adult ; Actinin/genetics ; Aryldialkylphosphatase/genetics ; Blood Glucose ; Cholesterol ; Diabetes Mellitus/genetics ; Genotype ; Hypertension/genetics ; Peptidyl-Dipeptidase A/genetics ; Polymorphism, Genetic/genetics ; Triglycerides
Chemical Substances	Actinin (11003-00-2) ; ACTN3 protein, human ; Aryldialkylphosphatase (EC 3.1.8.1) ; Blood Glucose ; Cholesterol (97C5T2UQ7J) ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; PON1 protein, human (EC 3.1.8.1) ; Triglycerides ; ACE protein, human (EC 3.4.15.1)
Language	English
Publishing date	2023-11-07
Publishing country	Brazil
Document type	Journal Article
ISSN	2359-4292
ISSN (online)	2359-4292
DOI	10.20945/2359-4292-2021-0204
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Article ; Online: Angiotensin-Ⅱ and angiotensin-(1-7) imbalance affects comorbidity of depression and coronary heart disease.

Han, Wenxiu / Wei, Zhijie / Dang, Ruili / Guo, Yujin / Zhang, Hailiang / Geng, Chunmei / Wang, Changshui / Feng, Qingyan / Jiang, Pei

Peptides

2020 Volume 131, Page(s) 170353

Abstract: ... single-nucleotide polymorphisms (SNPs) spanning the angiotensin converting enzyme 2 (ACE2) and MAS1 genes were genotyped ... Angiotensin-Ⅱ (Ang-Ⅱ) and angiotensin-(1-7) [Ang-(1-7)] are considered to exert biological effects ... A large body of evidence suggests a relationship between depression and coronary heart disease (CHD ...

Abstract	A large body of evidence suggests a relationship between depression and coronary heart disease (CHD). Angiotensin-Ⅱ (Ang-Ⅱ) and angiotensin-(1-7) [Ang-(1-7)] are considered to exert biological effects in both conditions. Here, we aimed to determine the role of Ang-Ⅱ and Ang-(1-7) in the occurrence of comorbid depression in patients with CHD. Our study included 214 CHD patients and 100 matched healthy controls. Serum Ang-Ⅱ and Ang-(1-7) levels were assessed by ELISA, and the depression symptoms were evaluated by the nine-item Patient Health Questionnaire (PHQ-9). Linear regression and correlation analyses were used to estimate the associations between PHQ-9 scores and Ang-Ⅱ and Ang-(1-7) serum levels. Six single-nucleotide polymorphisms (SNPs) spanning the angiotensin converting enzyme 2 (ACE2) and MAS1 genes were genotyped. The associations between SNPs and depression risk in CHD patients were examined using logistic regression analysis with adjustment for age and gender. Decreased Ang-(1-7) (P < 0.05) and an elevated Ang-Ⅱ/Ang-(1-7) ratio (P < 0.01) were observed in CHD patients with depression compared to CHD patients without depression. PHQ-9 scores were negatively correlated with Ang-(1-7) level (r=-0.44, P < 0.01) and positively correlated with the Ang-Ⅱ/Ang-(1-7) ratio (r = 0.33, P < 0.05). Furthermore, carriers of risk allele T for CHD with depression had significantly higher PHQ-9 scores (P < 0.05), lower Ang-(1-7) level (P < 0.01), and higher Ang-Ⅱ/Ang-(1-7) ratio (P < 0.05) than those CC carriers. Collectively, our results firstly showed that Ang-(1-7) serum level in CHD patients may protect against comorbid depression. Moreover, the imbalance between Ang-Ⅱ and Ang-(1-7) may contribute to depression in CHD patients.
MeSH term(s)	Adult ; Angiotensin I/blood ; Angiotensin I/genetics ; Angiotensin II/blood ; Angiotensin II/genetics ; Angiotensin-Converting Enzyme 2/blood ; Angiotensin-Converting Enzyme 2/genetics ; Case-Control Studies ; China/epidemiology ; Comorbidity ; Coronary Disease/blood ; Coronary Disease/epidemiology ; Coronary Disease/genetics ; Coronary Disease/physiopathology ; Depression/blood ; Depression/epidemiology ; Depression/genetics ; Depression/physiopathology ; Female ; Gene Expression Regulation ; Genotype ; Humans ; Linear Models ; Male ; Middle Aged ; Peptide Fragments/blood ; Peptide Fragments/genetics ; Polymorphism, Single Nucleotide ; Proto-Oncogene Proteins/blood ; Proto-Oncogene Proteins/genetics ; ROC Curve ; Receptors, G-Protein-Coupled/blood ; Receptors, G-Protein-Coupled/genetics ; Signal Transduction ; Surveys and Questionnaires
Chemical Substances	Peptide Fragments ; Proto-Oncogene Proteins ; Receptors, G-Protein-Coupled ; proto-oncogene proteins c-mas-1 ; Angiotensin II (11128-99-7) ; Angiotensin I (9041-90-1) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; angiotensin I (1-7) (IJ3FUK8MOF)
Language	English
Publishing date	2020-06-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	769028-9
ISSN	1873-5169 ; 0196-9781
ISSN (online)	1873-5169
ISSN	0196-9781
DOI	10.1016/j.peptides.2020.170353
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Article ; Online: Angiotensin converting enzyme genotypes and mortality from COVID-19: An ecological study.

Aung, Ar K / Aitken, Tess / Teh, Bing M / Yu, Christiaan / Ofori-Asenso, Richard / Chin, Ken L / Liew, Danny

The Journal of infection

2020 Volume 81, Issue 6, Page(s) 961–965

Abstract: Background: Angiotensin converting enzyme (ACE) genotypes are known to be associated ... genotype is highest in east Asian countries and lower among the European and African countries. An inverse ... 002-0.7, p = 0.03). However, no association was found between DD genotype frequency and COVID-19 ...

Abstract	Background: Angiotensin converting enzyme (ACE) genotypes are known to be associated with development of acute respiratory distress syndrome (ARDS) and resultant mortality. In the present study, we examined the association between distribution frequency of ACE genotypes and COVID-19 mortality. Methods: We undertook an ecological study to examine the association between ACE genotypes and COVID-19 mortality across 25 countries to represent different geographical regions of the world. The population frequencies of ACE genotypes were drawn from previously published reports and data on COVID-19-related mortality were extracted from 'Worldometer'. Multivariable analyses were also undertaken adjusting for age (median age), sex (percentage of females) and the number of COVID-19 tests undertaken. Associations between genotypes deletion/deletion (DD) and insertion/insertion (II) prevalence and COVID-19-related mortality (per million people per day since the first diagnosed case) were evaluated. Results: The frequency of II genotype is highest in east Asian countries and lower among the European and African countries. An inverse geographical distribution frequency was noted for DD genotype. Increasing II genotype frequency was significantly associated with decreased COVID-19 mortality rates (adjusted incident rate ratio [IRR] 0.3, 95% confidence interval [CI]: 0.002-0.7, p = 0.03). However, no association was found between DD genotype frequency and COVID-19 mortality rates (adjusted IRR 4.3, 95% CI: 0.5-41.2, p = 0.2). Conclusions: Distribution frequency of ACE insertion/insertion (II) genotype may have a significant influence on COVID-19 mortality. This information has potential utility for resource planning at a systemic level, as well as for clinical management.
MeSH term(s)	Angiotensin-Converting Enzyme 2/genetics ; COVID-19/genetics ; COVID-19/mortality ; Case-Control Studies ; Female ; Gene Frequency ; Genetic Predisposition to Disease/genetics ; Genotype ; Humans ; Male ; Peptidyl-Dipeptidase A/genetics ; Polymorphism, Genetic ; SARS-CoV-2
Chemical Substances	ACE protein, human (EC 3.4.15.1) ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Keywords	covid19
Language	English
Publishing date	2020-11-14
Publishing country	England
Document type	Journal Article
ZDB-ID	424417-5
ISSN	1532-2742 ; 0163-4453
ISSN (online)	1532-2742
ISSN	0163-4453
DOI	10.1016/j.jinf.2020.11.012
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Article: Angiotensin-Ⅱ and angiotensin-(1-7) imbalance affects comorbidity of depression and coronary heart disease

Han, Wenxiu / Wei, Zhijie / Dang, Ruili / Guo, Yujin / Zhang, Hailiang / Geng, Chunmei / Wang, Changshui / Feng, Qingyan / Jiang, Pei

Peptides. 2020 Sept., v. 131

2020

Abstract	A large body of evidence suggests a relationship between depression and coronary heart disease (CHD). Angiotensin-Ⅱ (Ang-Ⅱ) and angiotensin-(1-7) [Ang-(1-7)] are considered to exert biological effects in both conditions. Here, we aimed to determine the role of Ang-Ⅱ and Ang-(1-7) in the occurrence of comorbid depression in patients with CHD. Our study included 214 CHD patients and 100 matched healthy controls. Serum Ang-Ⅱ and Ang-(1-7) levels were assessed by ELISA, and the depression symptoms were evaluated by the nine-item Patient Health Questionnaire (PHQ-9). Linear regression and correlation analyses were used to estimate the associations between PHQ-9 scores and Ang-Ⅱ and Ang-(1-7) serum levels. Six single-nucleotide polymorphisms (SNPs) spanning the angiotensin converting enzyme 2 (ACE2) and MAS1 genes were genotyped. The associations between SNPs and depression risk in CHD patients were examined using logistic regression analysis with adjustment for age and gender. Decreased Ang-(1-7) (P < 0.05) and an elevated Ang-Ⅱ/Ang-(1-7) ratio (P < 0.01) were observed in CHD patients with depression compared to CHD patients without depression. PHQ-9 scores were negatively correlated with Ang-(1-7) level (r=-0.44, P < 0.01) and positively correlated with the Ang-Ⅱ/Ang-(1-7) ratio (r = 0.33, P < 0.05). Furthermore, carriers of risk allele T for CHD with depression had significantly higher PHQ-9 scores (P < 0.05), lower Ang-(1-7) level (P < 0.01), and higher Ang-Ⅱ/Ang-(1-7) ratio (P < 0.05) than those CC carriers. Collectively, our results firstly showed that Ang-(1-7) serum level in CHD patients may protect against comorbid depression. Moreover, the imbalance between Ang-Ⅱ and Ang-(1-7) may contribute to depression in CHD patients.
Keywords	alleles ; bioactive properties ; blood serum ; comorbidity ; coronary disease ; enzyme-linked immunosorbent assay ; gender ; genotyping ; mental depression ; patients ; peptidyl-dipeptidase A ; questionnaires ; regression analysis ; risk ; single nucleotide polymorphism
Language	English
Dates of publication	2020-09
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	769028-9
ISSN	1873-5169 ; 0196-9781
ISSN (online)	1873-5169
ISSN	0196-9781
DOI	10.1016/j.peptides.2020.170353
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Article ; Online: Genetic Associations With Plasma Angiotensin Converting Enzyme 2 Concentration: Potential Relevance to COVID-19 Risk.

Nelson, Christopher P / Sama, Iziah E / Codd, Veryan / Webb, Thomas R / Ye, Shu / Lang, Chim C / Voors, Adriaan A / Ng, Leong L / Samani, Nilesh J

Circulation

2020 Volume 142, Issue 11, Page(s) 1117–1119

MeSH term(s)	Aged ; Aged, 80 and over ; Alleles ; Angiotensin-Converting Enzyme 2 ; Betacoronavirus ; COVID-19 ; Chromosomes, Human, Pair 12/genetics ; Chromosomes, Human, Pair 21/genetics ; Chromosomes, Human, X/genetics ; Coronavirus Infections/blood ; Coronavirus Infections/enzymology ; Coronavirus Infections/epidemiology ; Coronavirus Infections/genetics ; Female ; Gene Expression Regulation, Enzymologic/genetics ; Gene Frequency ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Genotype ; Hepatocyte Nuclear Factor 1-alpha/genetics ; Humans ; INDEL Mutation ; Linkage Disequilibrium ; Male ; Middle Aged ; Pandemics ; Peptidyl-Dipeptidase A/biosynthesis ; Peptidyl-Dipeptidase A/blood ; Peptidyl-Dipeptidase A/genetics ; Pneumonia, Viral/blood ; Pneumonia, Viral/enzymology ; Pneumonia, Viral/epidemiology ; Pneumonia, Viral/genetics ; Polymorphism, Single Nucleotide ; Receptors, Virus/biosynthesis ; Receptors, Virus/blood ; Receptors, Virus/genetics ; Risk ; SARS-CoV-2 ; Sex Characteristics ; Sex Distribution ; Transcriptional Regulator ERG/genetics
Chemical Substances	ERG protein, human ; HNF1A protein, human ; Hepatocyte Nuclear Factor 1-alpha ; Receptors, Virus ; Transcriptional Regulator ERG ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Language	English
Publishing date	2020-07-07
Publishing country	United States
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	80099-5
ISSN	1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
ISSN (online)	1524-4539
ISSN	0009-7322 ; 0069-4193 ; 0065-8499
DOI	10.1161/CIRCULATIONAHA.120.049007
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Article ; Online: Angiotensin II type 1 receptor gene polymorphism and serum angiotensin-converting enzyme level in Egyptian children with systemic lupus erythematosus.

Shoaib, Rasha Mohamed Saleh / Hammad, Ayman / Yahia, Sohier / Elsaid, Afaf / Abdel-Malak, Camelia Adly

Clinical rheumatology

2018 Volume 37, Issue 12, Page(s) 3309–3317

Abstract: ... compared to controls (p ˂ 0.0001). There were no associations between AT1R gene polymorphism and serum ACE ... The frequencies of C-containing genotypes (AC + CC) and C-allele of AT1R (A1166C) were significantly higher in SLE ... genotypes and C-allele compared with controls (p ˂ 0.0001, OR = 5.1, 95% CI = 2.7-9.7; p ˂ 0.0001, OR = 3.5 ...

Abstract	Angiotensin II, the major effective molecule of the renin-angiotensin system, plays a vital role in the development of systemic lupus erythematosus (SLE). To study angiotensin II type 1 receptor (AT1R) gene polymorphism at (A1166C) in Egyptian children with SLE and its correlation with serum ACE level and SLE manifestations. AT1R gene polymorphism (A1166C) was done in 123 children with SLE in comparison to 100 healthy controls using polymerase chain reaction-based restriction fragment length polymorphism method (PCR-RFLP) and the tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) to confirm the results of the genotyping. Serum ACE level measurement was done using ELISA technique. The frequencies of C-containing genotypes (AC + CC) and C-allele of AT1R (A1166C) were significantly higher in SLE patients compared to controls (p < 0.0001, OR = 4.9, 95% CI = 2.7-8.8; p ˂ 0.0001, OR = 3.6, 95% CI = 2.2-5.9, respectively). Lupus nephritis (LN) patients had significantly higher frequency of (AC + CC) genotypes and C-allele compared with controls (p ˂ 0.0001, OR = 5.1, 95% CI = 2.7-9.7; p ˂ 0.0001, OR = 3.5, 95% CI = 2.1-6.02, respectively). Mean serum ACE levels were significantly higher in SLE patients compared to controls (p ˂ 0.0001). There were no associations between AT1R gene polymorphism and serum ACE level and the clinical manifestations of SLE. The AT1R gene polymorphism can be considered a risk factor for the development of SLE in Egyptian children.
MeSH term(s)	Adolescent ; Alleles ; Child ; Child, Preschool ; Cross-Sectional Studies ; Egypt/epidemiology ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Lupus Erythematosus, Systemic/blood ; Lupus Erythematosus, Systemic/genetics ; Lupus Nephritis/blood ; Lupus Nephritis/genetics ; Male ; Peptidyl-Dipeptidase A/blood ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; Receptor, Angiotensin, Type 1/genetics
Chemical Substances	Receptor, Angiotensin, Type 1 ; ACE protein, human (EC 3.4.15.1) ; Peptidyl-Dipeptidase A (EC 3.4.15.1)
Language	English
Publishing date	2018-08-09
Publishing country	Germany
Document type	Journal Article
ZDB-ID	604755-5
ISSN	1434-9949 ; 0770-3198
ISSN (online)	1434-9949
ISSN	0770-3198
DOI	10.1007/s10067-018-4255-3
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Article ; Online: Clinical impact of angiotensin I converting enzyme polymorphisms in subjects with resistant hypertension.

Imbalzano, Egidio / Vatrano, Marco / Quartuccio, Sebastiano / Di Stefano, Rossella / Aragona, Caterina Oriana / Mamone, Federica / D'Ascola, Angela / Scuruchi, Michele / Felice, Francesca / Trapani, Giovanni / Alibrandi, Angela / Ciconte, Vincenzo Antonio / Ceravolo, Roberto / Saitta, Antonino / Mandraffino, Giuseppe

Molecular and cellular biochemistry

2017 Volume 430, Issue 1-2, Page(s) 91–98

Abstract: ... renin-angiotensin system (RAS) activity and development of cardiovascular disease; significant associations between I/D ... Angiotensin I converting enzyme (ACE) insertion/deletion (I/D) polymorphism is thought to affect ... and I allele carriers. DD genotype appeared strongly associated with higher HOMA values (p < 0.001 ...

Abstract	Angiotensin I converting enzyme (ACE) insertion/deletion (I/D) polymorphism is thought to affect renin-angiotensin system (RAS) activity and development of cardiovascular disease; significant associations between I/D polymorphism and atherosclerosis, stroke, nephropathy, and early mortality were already found. We investigated whether Southern Italy resistant hypertensives presented an association between the presence of I and/or D alleles and early vascular damage, inflammation, and insulin resistance. One-hundred-fifty resistant hypertensives were enrolled, studied, and genotyped; carotid intima-media thickness (cIMT), arterial stiffness (AS), and HOMA indices were also evaluated. D allele was more prevalent, and 74 patients presented DD homozygosis. Sixty-eight patients had metabolic syndrome (MetS), without significant differences between DD and I allele carriers. DD genotype appeared strongly associated with higher HOMA values (p < 0.001), and also with both Augmentation Index (AIx, p = 0.003) and Pulse Wave Velocity (PWV, p = 0.023). A significant association was found between DD genotype and cIMT (p < 0.005), while no association between ACE genotype and the presence of carotid plaques. HOMA was correlated with AS (PWV: p < 0.001; AIx: p < 0.01). DD genotype appeared to be associated with AS and HOMA index, but not with inflammation, independently from blood pressure values and the presence of other MetS factors, confirming D allele as an independent risk marker. Vascular damage may develop and progress independently from other risk factors in resistant hypertensives, likely through the interplay between ACE gene, RAS activity, and insulin resistance.
Language	English
Publishing date	2017-06
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	184833-1
ISSN	1573-4919 ; 0300-8177
ISSN (online)	1573-4919
ISSN	0300-8177
DOI	10.1007/s11010-017-2957-5
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Article ; Online: DNA methylation and genetic variation of the angiotensin converting enzyme (ACE) in depression.

Lam, Dilys / Ancelin, Marie-Laure / Ritchie, Karen / Saffery, Richard / Ryan, Joanne

Psychoneuroendocrinology

2017 Volume 88, Page(s) 1–8

Abstract: ... This study provides evidence that associations between ACE methylation and depression are genotype-dependent ... with the angiotensin converting enzyme (ACE) a key regulator of the stress response. Epigenetic regulation of ACE ... Depression Scale (CES-D). Genotype information for seven polymorphisms across the ACE gene was also available ...

Abstract	Background: Depression is one of the most prevalent psychiatric disorders, and in older persons is associated with high levels of comorbidity and under-treatment. Dysfunction of the hypothalamic-pituitary-adrenal (HPA) stress axis is consistently observed in the older population as well as depressed patients, with the angiotensin converting enzyme (ACE) a key regulator of the stress response. Epigenetic regulation of ACE may play an important role in HPA axis (dys)regulation. Objective: To investigate ACE promoter methylation as a biomarker of late-life depression, and its association with genetic variation and cortisol secretion. Method: The longitudinal general population ESPRIT study is aimed at investigating psychiatric disorders in older persons (n=1863, average age=73). Depression was assessed using the Mini International Neuropsychiatric Interview according to DSM-IV criteria and the Centre for Epidemiologic Studies Depression Scale (CES-D). Genotype information for seven polymorphisms across the ACE gene was also available. Blood and saliva samples collected at baseline and used to extract DNA and measure cortisol, respectively. Sequenom MassARRAY was used to measure promoter DNA methylation of the ACE gene (n=552). Results: There was no evidence of an association between ACE promoter methylation and depression. However, there was evidence that ACE genetic variants influenced methylation, and modified the association between depression and methylation (Δ at various sites; -2.05% to 1.74%; p=0.019 to 0.039). Multivariate analyses were adjusted for participants' lifestyle, health and medical history. Independent of depression status, ACE methylation was inversely correlated with cortisol levels (r=-0.336, p=0.042). Conclusion: This study provides evidence that associations between ACE methylation and depression are genotype-dependent, suggesting that the development of reliable depression biomarkers may need to consider methylation levels in combination with underlying genetic variation. ACE methylation may also be a suitable biomarker of cortisol and/or HPA axis activity.
MeSH term(s)	Aged ; Aged, 80 and over ; Biomarkers/blood ; DNA Methylation/genetics ; Depression/genetics ; Epigenesis, Genetic ; Female ; Genetic Predisposition to Disease ; Genetic Variation/genetics ; Humans ; Hydrocortisone/analysis ; Hypothalamo-Hypophyseal System ; Longitudinal Studies ; Male ; Peptidyl-Dipeptidase A/genetics ; Peptidyl-Dipeptidase A/metabolism ; Pituitary-Adrenal System ; Polymorphism, Genetic/genetics ; Promoter Regions, Genetic/genetics ; Saliva/chemistry
Chemical Substances	Biomarkers ; ACE protein, human (EC 3.4.15.1) ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; Hydrocortisone (WI4X0X7BPJ)
Language	English
Publishing date	2017-11-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	197636-9
ISSN	1873-3360 ; 0306-4530
ISSN (online)	1873-3360
ISSN	0306-4530
DOI	10.1016/j.psyneuen.2017.11.003
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