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NFκB1 Polymorphisms Are Associated with Severe Influenza A (H1N1) Virus Infection in a Canadian Population
Suhrobjon Mullo Mirzo1, Anand Kumar2,3, Naresh Kumar Sharma2
1Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3X 0P3, Canada.
Insights
Genetic variations in the NFκB1 gene are linked to severe outcomes in Canadian patients with pandemic influenza A (H1N1). Specific NFκB1 gene polymorphisms may affect how individuals respond to H1N1 infection.
Area of Science:
- Genetics
- Immunology
- Virology
Background:
- The 2009 pandemic influenza A (H1N1) caused significant global health challenges.
- Understanding host genetic factors influencing H1N1 infection severity is crucial for public health.
- The NFκB1 gene plays a role in immune responses and inflammation.
Purpose of the Study:
- To investigate the association between NFκB1 gene polymorphisms and clinical outcomes in Canadian H1N1 patients.
- To identify specific genetic variations within NFκB1 that correlate with severe H1N1 infection.
Main Methods:
- Genotyping of the NFκB1 gene in 36 Caucasian ICU patients from the 2009 H1N1 pandemic.
- Utilized next-generation sequencing (Roche 454) for SNP discovery.
- Compared SNP frequencies with the 1000 Genomes Project British Caucasian population.
Main Results:
- Identified 136 single nucleotide polymorphisms (SNPs) in the NFκB1 gene.
- Found 63 SNPs significantly enriched in ICU patients compared to controls (p < 0.05).
- Enriched SNPs were predominantly intronic, with two non-transcribing exonic variants.
Conclusions:
- Genetic variations within the NFκB1 gene are associated with clinical outcomes of pandemic H1N1 infection.
- Sequence variations in NFκB1 may influence an individual's immune response and susceptibility to severe influenza.
- These findings highlight NFκB1 as a potential genetic marker for H1N1 infection severity.
Abstract:
Background: We examined associations between NFκB1 polymorphisms and influenza A (H1N1) clinical outcomes in Canadian. Methods: A total of thirty-six Caucasian patients admitted to the intensive care unit (ICU) in hospitals in Canada were recruited during the 2009 H1N1 pandemic. Genomic DNA was extracted from the whole blood samples. The NFkB1 gene was targeted for genotyping using next-generation sequencing technology—Roche 454. Results: A total of 136 single nucleotide polymorphisms (SNPs) were discovered within the NFκB1 gene. Among them, 63 SNPs were significantly enriched in patients admitted in the ICU (p < 0.05) compared with the British Caucasian population in the 1000 Genomes study. These enriched SNPs are mainly intron variants, and only two are exon SNPs from the non-transcribing portion of the NFκB1 gene. Conclusions: Genetic variations in the NFκB1 gene could influence clinical outcomes of pandemic H1N1 infections. Our findings showed that sequence variations of the NFκB1 gene might influence patient response to influenza infection.
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