Association of  ESR1  (rs2234693 and rs9340799),  CETP  (rs708272),  MTHFR  (rs1801133 and rs2274976) and  MS  (rs185087) polymorphisms with Coronary Artery Disease (CAD)

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

Coronary artery disease (CAD) is a complex disease resulting from the cumulative and interactive effects of large number of genes along with environmental exposure. Therefore, the present study was envisaged as an effort to study the association of candidate genes ESR1 (rs2234693 and rs9340799), CETP (rs708272), MTHFR (rs1801133 and rs2274976) and MS (rs185087) polymorphisms with the risk of CAD, targeting the populations of Jammu (JandK).

Method

A total of 400 confirmed CAD patients and 400 healthy controls were enrolled for the present study. Genotyping was done by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP).

Results

ESR1 gene (rs9340799) polymorphism was found to be associated with CAD in all the genetic models. The haplotype analysis of ESR1 (rs2234693 and rs9340799) gene revealed that C-G haplotype was conferring approximately 5-fold risk and T-A haplotype was adding 1.4-fold risk towards the disease. ‘T’ allele of MTHFR rs1801133 SNP was observed to be responsible for development of CAD in our study population ( p < 0.0001). In case of MTHFR (rs1801133 and rs2274976) gene, the haplotype T-G was observed to confer 4.7-fold risk towards CAD whereas haplotype C-G provided nearly a 1.7 fold protection towards development of CAD. For MS gene, rs185087 was also found to be associated with CAD in a co-dominant ( p = 0.003 and p = 0.03), dominant ( p = 0.001) and allelic models (p = 0.001). The gene-gene interaction revealed strong epistasis between single nucleotide polymorphisms (SNPs), ESR1 rs9340799 and MTHFR rs2274976. Furthermore, the dendrogram for gene-environment dataset indicated moderately synergistic interaction between CETP rs708272 and physical inactivity.

Conclusion

In the study under reference, a significant association of ESR1- XbaI (rs9340799), MTHFR C677T (rs1801133) and MS A2756G (rs185087) gene polymorphisms with the susceptibility of CAD in the population of Jammu region (JandK) has been observed.

Related collections

Most cited references 51

Record: found
Abstract: found
Article: not found

Estrogen signaling and cardiovascular disease.

Elizabeth Murphy (2011)

Estrogen has pleiotropic effects on the cardiovascular system. The mechanisms by which estrogen confers these pleiotropic effects are undergoing active investigation. Until a decade ago, all estrogen signaling was thought to occur by estrogen binding to nuclear estrogen receptors (estrogen receptor-α and estrogen receptor-β), which bind to DNA and function as ligand-activated transcription factors. Estrogen binding to the receptor alters gene expression, thereby altering cell function. Estrogen also binds to nuclear estrogen receptors that are tethered to the plasma membrane, resulting in acute activation of signaling kinases such as PI3K. An orphan G-protein-coupled receptor, G-protein-coupled receptor 30, can also bind estrogen and activate acute signaling pathways. Thus, estrogen can alter cell function by binding to different estrogen receptors. This article reviews the different estrogen receptors and their signaling mechanisms, discusses mechanisms that regulate estrogen receptor levels and locations, and considers the cardiovascular effects of estrogen signaling.

0 comments Cited 124 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Estrogen receptor alpha gene polymorphisms and risk of myocardial infarction.

Jacqueline Witteman, Albert Hofman, Rogier Nijhuis … (2004)

The role of estrogens in ischemic heart disease (IHD) is uncertain. Evidence suggests that genetic variations in the estrogen receptor alpha (ESR1) gene may influence IHD risk, but the role of common sequence variations in the ESR1 gene is unclear. To determine whether the ESR1 haplotype created by the c.454-397T>C (PvuII) and c.454-351A>G (XbaI) polymorphisms is associated with myocardial infarction (MI) and IHD risk. In 2617 men and 3791 postmenopausal women from The Rotterdam Study (enrollment between 1989-1993 and follow-up to January 2000), a population-based, prospective cohort study of participants aged 55 years and older, ESR1 c.454-397T>C and c.454-351A>G haplotypes were determined. Detailed interviews and physical examinations were performed, blood samples were obtained, and cardiovascular risk factors were assessed. The primary outcome was MI and IHD defined as MIs, revascularization procedures, and IHD mortality. Approximately 29% of women and 28.2% of men were homozygous carriers of the ESR1 haplotype 1 (-397 T and -351 A) allele, 49% of women and 50% of men were heterozygous carriers, and 22% of women and 21.4% of men were noncarriers. During a mean follow-up of 7.0 years, 285 participants (115 women; 170 men) had MI, and 440 (168 women; 272 men) had an IHD event, of which 97 were fatal. After adjustment for known cardiovascular risk factors, female heterozygous carriers of haplotype 1 had an increased risk of MI (event rate, 2.8%; relative risk [RR], 2.23; 95% confidence interval [CI], 1.13-4.43) compared with noncarriers (event rate, 1.3%), whereas homozygous carriers had an increased risk (event rate, 3.2%; RR, 2.48; 95% CI, 1.22-5.03). For IHD events, we observed a similar association. In women, the effect of haplotype 1 on fatal IHD was larger than on nonfatal IHD. In men, the ESR1 haplotypes were not associated with an increased risk of MI (event rate, 5.7%; RR, 0.93; 95% CI, 0.59-1.46 for heterozygous carriers; and event rate, 5.1%; RR, 0.82; 95% CI, 0.49-1.38 for homozygous carriers) compared with noncarriers (event rate, 5.8%) and were not associated with an increased risk of IHD. In this population-based, prospective cohort study, postmenopausal women who carry ESR1 haplotype 1 (c.454-397 T allele and c.454-351 A allele) have an increased risk of MI and IHD, independent of known cardiovascular risk factors. In men, no association was observed.

0 comments Cited 37 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

The 677 C/T MTHFR polymorphism is associated with essential hypertension, coronary artery disease, and higher homocysteine levels.

Yilmaz Ozbay, Necip Ilhan, Dilara Kaman … (2008)

Essential hypertension (EH) and cardiovascular disease are common, multifactorial disorders likely to be influenced by multiple genes of modest effect. The C677T methylenetetrahydrofolate reductase (MTHFR) gene polymorphism is related to MTHFR enzyme activity and to plasma homocysteine (Hcy) concentration. This study was designed to investigate an association of this polymorphism with coronary artery disease (CAD), EH, and healthy subjects. In this study, we measured serum folate, serum vitamin B12, and plasma homocysteine and determined the MTHFR C677T genotype of 78 patients with essential hypertension, 100 patients with coronary artery disease, and 100 healthy subjects. MTHFR genotypes were assessed by real-time polymerase chain reaction. CC, CT, and TT genotype frequencies were 52, 44.0, and 4.0% in patients with CAD, respectively. In patients with essential hypertension, the CC, CT, and TT genotype frequencies were 46.2, 41.0, and 12.8%, respectively. In control subjects, the CC, CT, and TT genotype frequencies were 72.0, 26.0, and 2.0%, respectively. The C allele was significantly more frequent in controls compared with patients with EH (p<0.05), and CC genotypes were more frequent in controls compared to patients with EH and CAD. Homocysteine level was higher in TT genotypes in CAD patients compared with CC and CT genotypes (p<0.01). MTHFR gene polymorphism is an independent risk factor for EH but not for CAD. The TT genotype of the 677C/T MTHFR polymorphism is associated with EH and CAD. In addition, TT genotypes had higher plasma Hcy levels in CAD patients compared with CC and CT genotypes. MTHFR gene polymorphism is an independent risk factor for EH but not for CAD.

0 comments Cited 32 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Rakesh Kumar Panjaliya:

ORCID: http://orcid.org/0000-0002-0015-6027

panjaliya82@gmail.com

Journal

Journal ID (nlm-ta): BMC Cardiovasc Disord

Journal ID (iso-abbrev): BMC Cardiovasc Disord

Title: BMC Cardiovascular Disorders

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2261

Publication date (Electronic): 18 July 2020

Publication date PMC-release: 18 July 2020

Publication date Collection: 2020

Volume: 20

Electronic Location Identifier: 340

Affiliations

[1 ]GRID grid.412986.0, ISNI 0000 0001 0705 4560, Institute of Human Genetics, University of Jammu, ; Jammu, JandK 180006 India

[2 ]GRID grid.412986.0, ISNI 0000 0001 0705 4560, Human Genetics Lab, Department of Zoology, , University of Jammu, ; Jammu, JandK India

[3 ]GRID grid.412997.0, ISNI 0000 0001 2294 5433, Department of Zoology, , Government Degree College, ; Samba, JandK India

[4 ]Department of Cardiology, Acharaya Shri Chander College of Medical Sciences (ASCOMS) and Hospital, Sidhra, Jammu, JandK India

Author information

Rakesh Kumar Panjaliya http://orcid.org/0000-0002-0015-6027

Article

Publisher ID: 1618

DOI: 10.1186/s12872-020-01618-7

PMC ID: 7368753

PubMed ID: 32682401

SO-VID: c66e85d2-ff49-49b7-839f-cad911cbea24

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 5 March 2020

Date accepted : 9 July 2020

Custom metadata

ScienceOpen disciplines: Cardiovascular Medicine

Keywords: cad,cetp,esr1,mthfr,ms,polymorphism

Data availability:

ScienceOpen disciplines: Cardiovascular Medicine

Keywords: cad, cetp, esr1, mthfr, ms, polymorphism

Comments

Comment on this article

scite_

Cited by 7

See all cited by

Most referenced authors 1,296

See all reference authors

Association of ESR1 (rs2234693 and rs9340799), CETP (rs708272), MTHFR (rs1801133 and rs2274976) and MS (rs185087) polymorphisms with Coronary Artery Disease (CAD)

Read this article at

Abstract

Background

Method

Results

Conclusion

Related collections

Karger: Cardiovascular System

Most cited references 51

Estrogen signaling and cardiovascular disease.

Estrogen receptor alpha gene polymorphisms and risk of myocardial infarction.

The 677 C/T MTHFR polymorphism is associated with essential hypertension, coronary artery disease, and higher homocysteine levels.

Author and article information

Contributors

Journal

Affiliations

Author information

Article

History

Categories

Custom metadata

Comments

Comment on this article

Similar content 510

Cited by 7

Most referenced authors 1,296