INFLUENCE OF INTERLEUKIN-6 (-174 G/C) SINGLE NUCLEOTIDE POLYMORPHISM ON SERUM IL-6 LEVELS IN PREMATURE CORONARY ARTERY DISEASE

Main Article Content

Wafa Munir Ansari
ABDUL K NAVEED
DILSHAD A KHAN

Abstract

ABSTRACT:

Objectives: Premature Coronary Artery Disease (PCAD) has taken the form of an epidemic in Pakistan and its incidence in young individuals is on the rise. The objective was to evaluate role of Interleukin-6 (-174 G/C) gene promoter polymorphism and the serum level of (IL-6) in the identification of PCAD.

 Methodology: The case-control study carried out at Army Medical College, Rawalpindi, Pakistan, from July, 2014 to Jan, 2015 in collaboration with University College London, UK. 150 patients <45 yrs of age with > 70% stenosis, in at least one coronary vessel on angiography, were labeled as cases. While 150 subjects who were angio-negative for disease were taken as controls. Genotyping was performed using Taqman Assay while serum IL-6 was measured using Enzyme Linked Immuno-sorbent Assay (ELISA).

Results:  Total 300 subjects participated in the study.  Mean ± SD age of PCAD patients was 40 ± 3.80 while in controls it was 38 ± 7.8 yrs. Serum IL-6 levels were significantly high in PCAD patients (p<0.01). In IL-6 -174 (G/C) polymorphism homozygous CC was significantly associated with occurrence of PCAD. Serum IL-6 levels were significantly higher in CC genotype subjects when compared to GC and GG (p<0.05). The serum IL-6 levels significantly correlated with the atherosclerotic burden (p<0.05). Sensitivity-specificity of IL-6 at cut off value of 3.7 ng/dl was 77% and 81% respectively.

Conclusion:   IL-6 has significant diagnostic potential for PCAD with moderately high sensitivity and specificity. IL-6 (-174 G/C) polymorphism CC genotype can aid in the risk prediction of PCAD.

Keywords:  Gene promoter polymorphism; Interleukin-6; Premature Coronary Artery Disease; Risk prediction;

 

Article Details

How to Cite
Ansari, W. M., A. K. NAVEED, and D. A. KHAN. “INFLUENCE OF INTERLEUKIN-6 (-174 G/C) SINGLE NUCLEOTIDE POLYMORPHISM ON SERUM IL-6 LEVELS IN PREMATURE CORONARY ARTERY DISEASE”. KHYBER MEDICAL UNIVERSITY JOURNAL, vol. 7, no. 4, Feb. 2016, p. 151, https://www.kmuj.kmu.edu.pk/article/view/147.
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Original Articles

References

REFERENCES:

Ait-Oufella H, Taleb S, Mallat Z, Tedgui A . Recent Advances on the Role of Cytokines in Atherosclerosis.Arteriosclerosis, Thrombosis, and Vascular Biology. 2011; 31: 969-979

KishimotoT. IL-6: from its discovery to clinical applications. International Immunology.2010;22(5):347–352.

Su D, Li Z, Li X, Chen Y, Zhang Y, Ding D,et al. Association between Serum Interleukin-6 Concentration and Mortality in Patients with Coronary Artery Disease. Mediators of Inflammation. 2013;Article ID 726178, 7 pages Research Article.

Shah T, Zabaneh D, Gaunt T, Swerdlow NI, Shah S, Talmud PJ, et al. Gene-Centric Analysis Identifies Variants Associated With Interleukin-6 Levels and Shared Pathways With Other Inflammation Markers. Circ Cardiovasc Genet.2013;6:163-170.

Sun GQ, Wu GD, Meng Y, Du B, Li YB . IL-6 gene promoter polymorphisms and risk of coronary artery disease in a Chinese population. Genet Mol Res.2014; 26;13(3):7718-24.

Maitra A, Shanker J, Dash D, John S, Sannappa PR, Rao VS, et al. Polymorphisms in the IL6 gene in Asian Indian families with premature coronary artery disease--the Indian Atherosclerosis Research Study. Thromb Haemost. 2008 May;99(5):944-50.

Bhanushali AA, Das BR. Promoter variants in interleukin-6 and tumor necrosis factor alpha and risk of coronary artery disease in a population from Western India. Indian Journal of Human Genetics.2013 ;19(4):430-436.

Hartman J, Frishman WH. Inflammation and atherosclerosis: a review of the role of interleukin-6 in the development of atherosclerosis and the potential for targeted drug therapy. Cardiol Rev. 2014 May-Jun;22(3):147-51.

Saremi A, Anderson RJ, Luo P, Moritz TE, Schwenke DC, Allison M et al. Association between IL-6 and the extent of coronary atherosclerosis in the veterans affairs diabetes trial (VADT). Atherosclerosis.2009;203(2):Pages 610–614.

Koenig W, Khuseyinova N. Biomarkers of Atherosclerotic Plaque Instability and Rupture. Arteriosclerosis, Thrombosis, and Vascular Biology.2007 ; 27: 15-26.

Ferroni P, Aantonello R, Franco R, Palmirotta R, Guadagni F, Davi G, et al. Prognostic significance of interleukin-6 measurement in the diagnosis of acute myocardial infarction in emergency department. Clinica Chimica Acta.2007 ; 381(2):151-6.

Mowafy A , El-Akabawy H, Hussein A, Abd El Hay A. Prognostic value of IL6 in young adults presenting with acute coronary syndrome .The Egyptian Heart Journal.2015;67(2): 151–158

Niu W, Liu Y, Qi Y ,Wu Z, Zhu D, Jin W. Association of interleukin-6 circulating levels with coronary artery disease: A meta-analysis implementing mendelian randomization approach. International journal of cardiology 2012; 157(2):243-52,2012.

Satti HS, Hussain S and Javed Q. Association of Interleukin-6 Gene Promoter Polymorphism with Coronary Artery Disease in Pakistani Families. The Scientific World Journal 2013; Article ID 538365, 6 pages.

Phulukdaree A, Khan S, Ramkaran P, Govender R, Moodley D and Chuturgoon AA.The Interleukin-6 -174 G/C Polymorphism Is Associated with Increased Risk of Coronary Artery Disease in Young South African Indian Men. Metabolic syndrome and related disorders. 2013; DOI: 10.1089/met.2012.0130

Reiner AP, Carlson CS, Ziv E,Iribarren C, Jaquish CE, Nickerson DA. Genetic ancestry, population sub-structure, and cardiovascular disease-related traits among African-American participants in the CARDIA Study. Hum Genet.2007 ;121(5):565-75.

Kanikowska D, Pyda M, Korybalska K, Grajek T, Lesiak M, Bręborowicz A,et al. Age-related limitations of interleukin-6 in predicting early mortality in acute ST-elevation myocardial infarction. Immunity & Ageing 2014; 11:23.

Lai CL, Ji YR, Liu XH, Xing JP, Zhao JQ. Relationship between coronary atherosclerosis plaque characteristics and high sensitivity C-reactive proteins, interleukin-6. Chin Med J (Engl). 2011 ;124(16):2452-6

Autieri MV. Pro- and Anti-Inflammatory Cytokine Networks in Atherosclerosis. ISRN Vascular Medicine 2012; Article ID 987629, 17 pages

Fenkci S, Rota S, Sabir N,Sermez Y, Guclu A, Akdag B. Relationship of serum interleukin-6 and tumor necrosis factor alpha levels with abdominal fat distribution evaluated by ultrasonography in overweight or obese postmenopausal women. J Investig Med. 2006 ;54(8):455-60.

Khaodhiar, LLing P, Blackburn GL, Bistrain BR. Serum Levels of Interleukin-6 and C-Reactive Protein Correlate With Body Mass Index Across the Broad Range of Obesity. J Parenter Enteral Nutr. 2004; 28(6):410-415

Hacievliyagil SS, Mutlu LC, Temel I. Airway inflammatory markers in chronic obstructive pulmonary disease patients and healthy smokers. Niger J. Clin Pract.2013;16(1):76-81

Garcia-Rio F, Miravitlles M, Soriano JB, Muñoz L, Duran-Tauleria E, Sánchezet G al. Systemic inflammation in chronic obstructive pulmonary disease: A population-based study. Respir Res. 2010;11:63.