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Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journalsNo manuscriptsNo authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."
Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011
Dr. Shankar P.R.
"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."
Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011 Anuradha
Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.
Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020
Original article / research
Full Version
Chemokine Receptor Gene (CCR5) Polymorphism in Acute Coronary Syndrome: A Cross-sectional Study
Correspondence Address :
Dr. Sharan Badiger,
Professor and Head, Department of Medicine, Shri B.M. Patil Medical College, Hospital and Research Centre, BLDE (Deemed to be University), Vijayapura-586103, Karnataka, India.
E-mail: sharanrb@rediffmail.com
Introduction: Acute coronary syndrome is a multifactorial disease with a complex pathogenesis, mainly resulting from the interplay of genetic and environmental risk factors. Chemokines and their receptors play crucial roles in the initiation and progression of atherosclerosis. Chemokine Receptor 5 (CCR5) is an important mediator of leukocyte recruitment and leukopedesis. Most studies conducted on the relationship between CCR5 gene polymorphism and coronary artery disease in different regions and populations worldwide show conflicting results.
Aim: To investigate the genetic polymorphism of CCR5 genes associated with patients with acute coronary syndrome in the Vijayapura population.
Materials and Methods: A cross-sectional study was conducted at BLDE (Deemed to be University) Shri B.M. Patil Medical College Hospital and Research Centre, Vijayapura, Karnataka, India, involving patients admitted for acute coronary syndrome. A total of 100 patients were admitted with acute coronary syndrome. Nineteen patients with diabetes mellitus were excluded from the study based on the exclusion criteria. Clinical history, examination, electrocardiographic assessments, laboratory profiles, and blood samples were taken for the analysis of CCR5 gene polymorphism as part of the work-up. Patients were classified into two groups: one with the presence of CCR5 polymorphism as Group A (n=6), and the other without polymorphism as Group B (n=75). Parameters such as age, sex, occupation, lipid profile, renal function tests, and CCR5 polymorphism were studied between the groups. The data were statistically analysed. Categorical variables between the two groups were compared using the Chi-square test. Normally distributed continuous variables were compared using independent t-test, and non normally distributed variables were compared using the Mann-Whitney U test.
Results: In the present study, the most common age group was 50-70 years with a male predominance of 60.7%. Most of the patients in the study group were farmers (34.7%), followed by housewives (32%) and businessmen (14.7%). The most common risk factors observed in both study groups were smoking and tobacco chewing. Gene sequencing revealed CCR5 gene polymorphism in six out of 81 patients who were labelled as Group A, indicating an incidence of 7.5% (p<0.001). Out of the six positive patients in Group A, three were males and three were females. One patient was 45 years old, while the remaining five were above 60 years old.
Conclusion: The present study demonstrates a positive association between CCR5 polymorphism and acute coronary syndrome, indicating that the study population is genetically susceptible to the disease. By screening for high-risk individuals, better and more effective early interventions can be planned, thereby reducing the social burden, morbidity, and mortality associated with the disease.
Atherosclerosis, Coronary artery disease, Diabetes mellitus, Inflammatory mediators
As per the Global Burden of Disease study, it is estimated that 24.8% of all deaths in India are attributable to Cardiovascular Disease (CVD). According to the present study, the age-standardised CVD death rate in India is 272 per 100,000 people, which is higher than the global death rate of 235 per 100,000 people (1). Many predisposing risk factors have been identified for Acute Coronary Syndrome (ACS), including non modifiable factors such as age, sex, ethnicity, family history, and genetic factors, as well as modifiable factors such as hypertension, diabetes mellitus, smoking/tobacco use, obesity, and diet (2).
Atherosclerosis is a chronic inflammatory condition that worsens over time. It is characterised by the accumulation of lipids in the intima of blood vessel walls, endothelial dysfunction, and vascular inflammation (3). When the endothelium is damaged, inflammatory cells, particularly monocytes, migrate into the subendothelium where they differentiate into macrophages. Macrophages release chemoattractants, cytokines (such as chemokines and interleukins), and matrix metalloproteinases, enzymes that break down the extracellular matrix and contribute to plaque disruption (4). Chemokines play a crucial role in the pathogenesis of atherosclerosis, which is a risk factor for coronary heart disease. Detecting CCR5 polymorphism can help establish its role in acute coronary syndrome (5),(6).
Leukocytes produce soluble proteins called chemokines, which bind to G-protein-coupled receptors located in the lipid layer of the cell surface. These receptors consist of seven transmembrane domains (7TM) (7). The CCR5 gene is predominantly found in endothelial and immune cells and is located on chromosome 3P21.3 (8). Chemokines are produced by immune cells such as macrophages, neutrophils, mast cells, eosinophils, dendritic cells, and epithelial cells. After recognising their receptors, chemokines bind to the N-terminus part of the chemokine and activate the receptor (9).
The CCR5delta32 allele has been associated with reduced susceptibility to coronary artery disease, delayed onset of coronary heart disease in women, and protection against myocardial infarction (10). According to a study conducted by Hyde CL et al., in 2010, the CCR5delta32 polymorphism is linked to higher plasma levels of high-density lipoprotein cholesterol and lower levels of triglycerides, both of which contribute to a decreased risk of cardiovascular disease (11).
Fractalkine, acting at CX3CR1, appears to support chronic monocyte adherence and survival within the plaque, while CCL5, acting at CCR5, is thought to be essential for monocyte recruitment during the development of atherosclerosis (12). In an in-vivo study, it was observed that suppression of CCL2, CX3CR1, and CCR5 had additive effects in reducing atherosclerosis. Targeting all three systems was necessary for nearly complete eradication of the disease in an atherosclerotic mouse model. CCR5 signalling controls the recruitment of monocytes to the plaques (13).
Monocytes play a significant role in atherosclerosis, and there is a CCR2-CX3CR1++Ly-6Clo monocytosis that is independent of CCR2 and CX3CR1 but relies on CCR5 signaling for monocyte entry into lesions and recruitment of T cells into established plaques (14),(15). Patients with coronary artery disease have peripheral blood mononuclear cells with elevated expression of CCL3 and CCL4, which act on CCR5 to worsen atherosclerosis. This effect can be reduced by statin medication (16). However, the available studies on CCR5 polymorphism and coronary artery disease have shown conflicting results (17),(18),(19),(20).
Two similar studies conducted on the Indian population were carried out in the North Indian population (21). These studies influenced us to investigate the genetic polymorphism of CCR5 genes associated with patients with acute coronary syndrome in the Vijayapura population.
The present cross-sectional study was conducted in the Department of General Medicine at BLDE (Deemed to be University) Shri B.M. Patil Medical College, Hospital, and Research Centre in Vijayapura, Karnataka, India. The study spanned from January 2020 to June 2022 and involved 100 patients admitted to the hospital with acute coronary syndrome. Prior to conducting the study, it received approval from the Institutional Ethical Committee (IEC/NO-09/2021 dated-22/01/2021), and it is registered in the Clinical Trial Registry-India (CTRI/2021/04/032889 dated-16/04/2021). The patients were given detailed explanations about the procedure, and consent was obtained.
Inclusion and Exclusion criteria: The inclusion criteria for the study were patients admitted with ST segment elevation myocardial infarction, non ST segment elevation myocardial infarction, and unstable angina. Patients with diabetes mellitus were excluded from the study.
Sample size calculation: The sample size was calculated based on an anticipated proportion of 5.2% of CCR5 among acute Myocardial Infarction (MI) patients, resulting in a required sample size of 81 patients, with a 95% level of confidence and 10% absolute precision (5). The formula used for sample size calculation was:
n=z2p*q/d2
where Z is the Z statistic at the α level of significance,
d2=Absolute error
P=Proportion rate
q=100-p
Study Procedure
Baseline investigations, including complete blood count, random blood glucose, renal function tests, lipid profile, serum electrolytes, and urine examination, were conducted. Additionally, cardiac-specific investigations such as Troponin I, Creatinine Phosphokinase-MB, Electrocardiogram, Chest X-ray, and 2-Dimensional Echocardiography were performed. A peripheral blood sample of 1 mL was collected from each patient for analysing CCR5 polymorphism. Out of the 100 patients admitted with acute coronary syndrome, 19 patients with diabetes mellitus were excluded based on the exclusion criteria. The patients were then divided into two groups: Group A (n=6) with the presence of CCR5 polymorphism, and Group B (n=75) without the polymorphism, as shown in (Table/Fig 1).
Genotyping: From 300 μL of peripheral blood, genomic Deoxyribonucleic Acid (DNA) was isolated using a commercial DNA isolation kit (Bangalore Genei, India). The primer sequences used for amplification are shown below:
Forward: 5’-CTCCCAGGAATCATCTTTACC-3’
Reverse: 5’-TCATTTCGACACCGAAGCAG-3’ (22).
The Polymerase Chain Reaction (PCR) reaction was conducted in a 20 μL reaction volume, which included 2 μL of genomic DNA (ranging from 50 ng/μL to 100 ng/μL), 0.4 μL of each primer (5 pmol), 0.4 μL of dNTP (10 pmol), 0.1 μL of Taq DNA polymerase (5 units/μL), 2 μL of Taq Buffer (5X) (Takara, Japan). The total volume was adjusted to 20 μL using molecular biology grade water. After PCR amplification, the amplicons were subjected to 1% agarose gel electrophoresis, and the DNA bands were observed using gel documentation.
Sequencing run: The prepared samples were analysed on an ABI 3730 genetic analyser (Applied Biosystems, USA) to generate DNA sequences. After the sequencing reaction was completed, the quality of the generated sequences was checked using Sequencing Analysis v5.4 software (Applied Biosystems, USA).
Sequence alignment: The generated sequences were aligned with their respective reference sequences using Variant Reporter software (ABI v1.1). This software performs sequence comparisons to identify novel mutations, known variants, insertions, and deletions. The results from the variant reporter were tabulated in PDF format, which is the default output format of the software program.
Statistical Analysis
The obtained data was entered into a Microsoft excel sheet, and statistical analysis was conducted using the Statistical Package for the Social Sciences (SPSS, version 20.0). The results were presented as Mean (Median)±Standard Deviation (SD), counts and percentages, and diagrams. For normally distributed continuous variables, a comparison between two groups was performed using an independent t-test. For non normally distributed variables, the Mann-Whitney U test was utilised. Categorical variables between the two groups were compared using the Chi-square test. A p-value of less than 0.05 was considered statistically significant. All statistical tests were performed as two-tailed tests.
Out of the 81 patients studied, the most common age group in Group-A was 60-69 years, while in Group-B it was 50-59 years, with a significant p-value of 0.001, as shown in (Table/Fig 2). Among the study participants, the majority were farmers (34.7%), followed by housewives (32%) and businessmen (14.7%). Other parameters such as haemoglobin, lipid profile, serum creatinine, serum electrolytes, and blood sugar were compared between the study groups and are tabulated in (Table/Fig 3). The present study observed a high incidence of smoking and tobacco chewing as risk factors for acute coronary syndrome in both study groups. The overall sex distribution showed a male predominance, with 53 male patients (60.7%) and 28 female patients (39.3%), as shown in (Table/Fig 4).
Out of the 81 patients, blood samples were analysed for CCR5 polymorphism. Six patients (7.4%) tested positive, while 75 patients (92%) tested negative, as shown in (Table/Fig 5). Among the six positive patients in Group-A, five of them had a frameshift mutation, as shown in [Table/Fig-6,7], which displays one of the frameshift mutations. The distribution of polymorphism among males and females was equal among the six positive cases in Group-A. The base position in genomic DNA for all six positive mutations ranged from 8250 to 340, within a narrow range, and no novel polymorphism was observed.
Regarding Electrocardiogram (ECG) findings, out of the 81 patients, Group-A had three patients with ST elevation in the inferior leads (II, III, aVF), and one patient each with Left Bundle Branch Block (LBBB), Non-ST-elevation Myocardial Infarction (NSTEMI), and lateral wall STEMI. In Group-B, the most common ECG finding was NSTEMI (22 patients, 29.3%), followed by ST elevation in the inferior leads (II, III, aVF) (20 patients, 26.7%), ST segment elevation in anterolateral leads (V3-V6, I, aVL) (12 patients, 16%), and unstable angina (2 patients, 2.7%).
In Group-A, consisting of six cases, Left Ventricular Ejection Fraction (LVEF) was observed to be <40% in 3 patients (50%) and >40% in 3 patients (50%). In Group-B, consisting of 75 cases, LVEF was <40% in 42 patients (56%) and >40% in 33 patients (44%).
In the present study, the most common age group was 60-69 years, which was similar to a study conducted by Kobayashi A et al., on 190 patients hospitalised with acute coronary syndrome between January 2007 and December 2013. They observed that the common age group was 60-70 years (23). Age is an important non modifiable risk factor and indicates that atherosclerosis is a disease that primarily affects the elderly.
In the present study, the sex distribution showed a male predominance of 53 patients (60.7%) and female patients of 28 (39.3%), which is similar to a study conducted by Sharma R et al., in 2014 on 1562 South Indian patients. They found that the majority were male, with 1242 (79.5%) and the remaining being females, with 320 (20.5%) (24). This can be attributed to the fact that modifiable risk factors such as smoking and alcohol consumption are more prevalent in males.
Regarding modifiable risk factors, the present study found that smoking was present in 30 patients (37%) and tobacco chewing in 31 patients (38.2%), similar to a study conducted by Rao V et al., in 2017 on 100 patients with acute coronary syndrome. They found that smoking was present in 61% of patients and alcohol consumption in 29% of patients (25). Therefore, there is a need for policies to control tobacco use, promote a healthy diet, and educate patients regarding the adverse effects of tobacco use, which can help improve the life expectancy of patients with acute coronary syndrome.
Out of the six positive cases in Group-A, there was an equal distribution of the polymorphism among males and females. In a 2006 study by Sharda S et al., on CCR5 deletion polymorphism in North Indian patients with coronary artery disease, they found a three times higher frequency of the polymorphism in CAD patients compared to normal individuals (21). Similarly, a 2011 study by Singh N et al., showed similar results with a four times higher frequency of the polymorphism in acute myocardial infarction patients (5). In a 2008 study by Afzal AR et al., conducted in the Bruneck population, the polymorphism was associated with significantly lower carotid intima-media thickness in the common carotid artery and a reduced incidence of cardiovascular disease (17). In 2001, González P et al., discussed genetic variation at the CCR5/CCR2 in myocardial infarction and found that patients carrying the ?ccr5-allele would be protected against an early episode of MI (18).
Similarly, other studies conducted outside of India in Spain, Czech Republic, Germany, and Hungary have shown a lower frequency of the polymorphism in CAD patients, concluding a protective role in their respective ethnicities and populations (6). The two Indian studies conducted in the North Indian population, as explained above, showed a significant positive association between CCR5 polymorphism and coronary artery disease, with no protective role (21). The present study is the first to be conducted in the South Indian population, showing evidence of CCR5 polymorphism in acute coronary syndrome patients.
Limitation(s)
The present study was conducted with a smaller study group. Future studies with a larger group can provide a better understanding of CCR5 polymorphism in acute coronary syndrome.
Genetic studies of diseases are gaining more popularity and importance in order to study the diseases in detail. The present study shows the expression of CCR5 polymorphism in patients with acute coronary syndrome. Screening for CCR5 polymorphism in high-risk individuals helps in risk modification and effective early intervention for these individuals, thereby minimising the social burden, morbidity, and mortality associated with the disease.
DOI: 10.7860/JCDR/2023/65263.18765
Date of Submission: May 06, 2023
Date of Peer Review: Jun 29, 2023
Date of Acceptance: Aug 28, 2023
Date of Publishing: Nov 01, 2023
AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. NA
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ETYMOLOGY: Author Origin
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