1. Association between -174G/C promoter polymorphism of the Interleukin-6 gene and ischemic stroke: A meta-analysis
Pradeep Kumar, Amit Kumar, Ram Sagar, Achal Kumar Srivastava, Kameshwar Prasad
Department of Neurology
All India Institute of Medical Sciences, New Delhi
RESULTS:
INTRODUCTION:
Stroke -Second common most leading cause of disability and death worldwide after ischemic heart disease (IHD)
IL-6- Major pleiotropic pro-inflammatory cytokines & key mediator in the inflammatory response to ischemic stroke
IL G/C polymorphisms- Creates a potential binding site for the transcription nuclear factor (NF)-1, resulting in repressed gene expression
G allele, on the other hand, is associated with higher circulating IL-6 levels
Many studies- focused on the potential genetic effects of IL G/C promoter polymorphisms but their association with the risk of ischemic stroke remains controversial and ambiguous
OBJECTIVES:
To investigate the association between IL G/C promoter polymorphism and with ischemic stroke
METHODS:
Electronic databases (PubMed) were searched until December 2013 for all case-control studies evaluating IL G/C promoter gene polymorphism and ischemic stroke in humans
All published manuscripts up until and including letters, previous meta-analyses and abstracts were included
The retrieved studies were examined thoroughly to assess their appropriateness for inclusion in our study
Search terms-‘inflammatory gene’, ‘Interleukin-6’, ‘polymorphism’, ‘ischemic stroke’, ‘cerebral infarction’, ‘brain infarction’ and ‘cerebrovascular accident’
In addition, reference lists were also examined to acquire additional relevant articles
STATISTICAL ANALYSIS:
Data were analyzed using software for preparing and maintaining Cochrane reviews (Review Manager, version 5.1)
HWE was evaluated by the Chi-square test
For Interleukin-6 (IL-6) gene variant, pooled odds ratio (OR) and 95% confidence interval (CI) was calculated.
Heterogeneity was examined using Higgins I-squared, Tau-squared and Chi-squared
RESULTS:
13 studies cases and 2665 controls
IL G/C and IS -not associated with the risk of ischemic stroke under both models
Dominant model [OR=1.03; 95% CI= ]
Recessive model [OR=0.98; 95%CI= ]
INCLUSION & EXCLUSION CRITERIA:
Studies were selected if:
published case-control studies focusing on the association between -174G/C IL-6 gene polymorphism and IS
confirmed the diagnosis of ischemic stroke by neuroimaging ( CT/MRI)
studies with full text written in English
studies that follow the Hardy Weinberg Equilibrium (HWE)
Studies were excluded if :
-Patients were children (age <18 years)
- Genotype frequencies was not reported
- Quantitative traits or intermediate phenotypes
CONCLUSION:
Our meta-analysis suggests IL G/C promoter polymorphisms were unlikely to be associated with risk of ischemic stroke
Further well-designed prospective large-scale studies are warranted