NFκB1 Polymorphisms Are Associated with Severe Influenza A (H1N1) Virus Infection in a Canadian Population
Abstract
:1. Introduction
2. Materials and Methods
2.1. The Studied Subjects
2.2. PCR Amplification and Sequencing of NFκB1 Gene
2.3. Sequence Analysis
2.4. Statistical Analysis
3. Results
3.1. Population Description
3.2. The Polymorphism of the NFκB1 Gene in the ICU Patients
3.3. Association of SNPs Genotypes with Severe Response to H1N1 Infection
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Variables | H1N1pdm09 (n = 36) |
---|---|
Ethnicity (%) | Caucasian (100%) |
Gender | |
Male | 19 (52.78%) |
Female | 17 (47.22%) |
Age (years) | |
<25 | 2 (5.67%) |
25–49 | 12 (33.33%) |
50–64 | 17 (47.22%) |
>65 | 5 (13.89%) |
Average | 50.76 + 14.13 |
Pregnancy | 2 (5.67%) |
Comorbidity | |
Obesity | 5 (13.89%) |
Diabetes Mellitus | 9 (25.00%) |
Hypertension | 17 (47.22%) |
Coronary heart disease | 1 (2.78%) |
Congestive heart failure | 3 (8.33%) |
Chronic obstructive | 5 (13.89%) |
pulmonary disease | |
Asthma | 7 (19.44%) |
Immunosuppression | 1 (2.78%) |
Invasive Ventilation (%) | |
Apache II Score | 22.12 ± 6.79 |
Death Rate | 0.41 ± 0.19 |
SNP ID | Chromosome Location | Minor Allele | MAF a | p Value | Phenotype d | |
---|---|---|---|---|---|---|
ICU b | GBR c | |||||
rs1599961 | 103443569 (intronic) | G | 0.18 | 0.46 | 1.53 × 10−7 | Cardiovascular, hypertension, |
rs1585215 | 103444474 (intronic) | C | 0.28 | 0.38 | 1.53 × 10−2 | Hodgkin lymphoma |
rs1585213 | 103444698 (intronic) | T | 0.38 | 0.46 | 9.78 × 10−3 | measles vaccine effectiveness, various diseases |
rs1598856 | 103446115 (intronic) | A | 0.50 | 0.57 | 4.82 × 10−2 | Cholangitis, ovarian cancer, gastric cancer |
rs230535 | 103448582 (intronic) | A | 0.51 | 0.62 | 6.11 × 10−3 | Bipolar disease |
rs170731 | 103448903 (intronic) | T | 0.39 | 0.62 | 1.30 × 10−6 | lymphedema, inflammatory reactions |
rs230534 | 103449041 (intronic) | T | 0.32 | 0.62 | 3.36 × 10−8 | Maculopathy, biliary and crohn’s disease |
rs230533 | 103450083 (intronic) | A | 0.44 | 0.62 | 8.10 × 10−5 | crohn’s disease |
rs230532 | 103450167 (intronic) | T | 0.54 | 0.62 | 3.83 × 10−2 | Hepatitis C, PBC, breast cancer inflammation |
rs230531 | 103450377 (intronic) | G | 0.35 | 0.62 | 2.24 × 10−9 | PBC, ovarian cancer, gastric cancer |
rs230530 | 103453980 (regulatory) | G | 0.18 | 0.43 | 2.41 × 10−3 | Hepatitis C, gastric cancer, allergic rhinitis |
rs230529 | 103457418 (regulatory) | C | 0.19 | 0.55 | 2.09 × 10−7 | drug addictions, schizophrenia, psychosis |
rs230528 | 103457585 (regulatory) | G | 0.19 | 0.55 | 1.60 × 10−8 | lung disease, coronary artery disease |
rs230526 | 103458825 (exonic) | G | 0.25 | 0.55 | 7.88 × 10−5 | metabolic variation, cytokine variation |
rs230525 | 103458877 (exonic) | G | 0.38 | 0.62 | 3.08 × 10−5 | liver cancer |
rs4648004 | 103461107 (intronic) | G | 0.11 | 0.32 | 6.08 × 10−3 | cerebrovascular, cardiovascular |
rs230523 | 103462038 (intronic) | C | 0.11 | 0.62 | 0.00 × 100 | various diseases |
rs118882 | 103463007 (regulatory) | T | 0.39 | 0.62 | 1.23 × 10−6 | allergic rhinitis |
rs230521 | 103463328 (regulatory) | C | 0.26 | 0.55 | 6.59 × 10−5 | breast cancer, hepatitis c, colorectal cancer, |
rs230520 | 103465612 (intronic) | G | 0.44 | 0.62 | 6.27 × 10−4 | PBC |
rs230519 | 103466749(intronic) | T | 0.44 | 0.62 | 6.10 × 10−4 | PBC, Tuberculosis |
rs93059 | 103468518 (intronic) | A | 0.11 | 0.42 | 1.51 × 10−5 | various diseases |
rs230493 | 103486216 (regulatory) | A | 0.42 | 0.62 | 2.89 × 10−4 | thyroid cancer, PBC, antipsychotic response |
rs35680095 | 103486698 (regulatory) | A | 0.03 | 0.12 | 3.66 × 10−2 | atopic asthma |
rs230494 | 103486969 (regulatory) | A | 0.29 | 0.55 | 7.03 × 10−4 | various diseases |
rs230496 | 103488491 (intronic) | G | 0.31 | 0.55 | 3.16 × 10−3 | liver cancer |
rs230498 | 103489603 (intronic) | A | 0.44 | 0.63 | 2.89 × 10−3 | ovarian cancer, gastric cancer |
rs230500 | 103491724 (intronic) | A | 0.40 | 0.63 | 8.34 × 10−5 | cytokine regulation |
rs230539 | 103495532 (regulatory) | G | 0.36 | 0.6 | 3.24 × 10−8 | ovarian cancer, gastric cancer |
rs1598858 | 103506095 (intronic) | G | 0.18 | 0.4 | 1.82 × 10−4 | kidney inflammation, cytokine regulation, |
rs3774956 | 103508526 (regulatory) | T | 0.31 | 0.48 | 3.77 × 10−3 | lymphedema, cytokine regulation, |
rs4648045 | 103508703 (regulatory) | C | 0.29 | 0.41 | 3.80 × 10−3 | various diseases |
rs3774959 | 103511114 (intronic) | A | 0.19 | 0.41 | 4.48 × 10−5 | Asthma, glioma, cytokine regulation, |
rs4698858 | 103513073 (intronic) | - | 0.36 | 0.48 | 3.62 × 10−2 | cytokine regulation |
rs11722146 | 103524629 (intronic) | - | 0.19 | 0.35 | 3.24 × 10−3 | colon and rectal cancer, colorectal cancer, |
rs12509403 | 103525350 (intronic) | T | 0.18 | 0.35 | 7.08 × 10−4 | kidney inflammation, allergic rhinitis |
rs12509517 | 103525508 (intronic) | C | 0.19 | 0.35 | 3.18 × 10−3 | colorectal cancer, gastric cancer |
rs3774968 | 103531112 (intronic) | A | 0.49 | 0.6 | 2.84 × 10−3 | plasma cell leukemia, vte, ovarian cancer, |
SNP ID | Alleles (Ref/Alt) | ICU | GBR | Adjusted p Value | SNP ID | Alleles (Ref/Alt) | ICU | GBR | Adjusted p Value | ||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
RAF | AAF | RAF | AAF | RAF | AAF | RAF | AAF | ||||||
rs1599961 | G/A | 0.03 | 0.2 | 0.5 | 0.2 | 1.53 × 10−7 | rs230497 | T/A | 0.06 | 0.2 | 0.5 | 0.4 | 0.00 × 100 |
rs1585215 | T/C | 0.22 | 0.2 | 0.5 | 0.1 | 1.53 × 10−2 | rs230498 | A/G | 0.28 | 0.3 | 0.5 | 0.4 | 2.89 × 10−3 |
rs1585214 | T/C | 0.08 | 0.3 | 0.5 | 0.3 | 2.29 × 10−6 | rs230499 | T/G | 0.06 | 0.3 | 0.5 | 0.4 | 5.60 × 10−9 |
rs1585213 | C/T | 0.19 | 0.3 | 0.5 | 0.2 | 9.78 × 10−3 | rs230500 | A/G | 0.19 | 0.3 | 0.5 | 0.4 | 8.34 × 10−5 |
rs1598856 | A/G | 0.28 | 0.4 | 0.5 | 0.3 | 4.82 × 10−2 | rs230502 | A/G | 0.25 | 0.1 | 0.5 | 0.2 | 9.77 × 10−4 |
rs230535 | A/C | 0.25 | 0.4 | 0.5 | 0.4 | 6.11 × 10−3 | rs230503 | G/A | 0.25 | 0.3 | 0.5 | 0.4 | 1.96 × 10−3 |
rs170731 | T/A | 0.11 | 0.3 | 0.5 | 0.4 | 1.30 × 10−6 | rs230538 | C/T | 0.17 | 0.2 | 0.5 | 0.3 | 4.38 × 10−5 |
rs230534 | T/C | 0.08 | 0.3 | 0.5 | 0.4 | 3.36 × 10−8 | rs230539 | G/A | 0.06 | 0.3 | 0.5 | 0.3 | 3.24 × 10−8 |
rs230533 | A/G | 0.17 | 0.4 | 0.5 | 0.4 | 8.10 × 10−5 | rs1598858 | A/G | 0.14 | 0.1 | 0.5 | 0.1 | 1.82 × 10−4 |
rs230532 | T/A | 0.31 | 0.4 | 0.5 | 0.4 | 3.83 × 10−2 | rs1598859 | T/C | 0.28 | 0.1 | 0.5 | 0.1 | 3.44 × 10−2 |
rs230531 | G/A | 0.03 | 0.3 | 0.5 | 0.4 | 2.20 × 10−9 | rs3774956 | C/T | 0.22 | 0.2 | 0.5 | 0.2 | 3.77 × 10−3 |
rs230530 | A/G | 0.31 | 0 | 0.5 | 0.2 | 2.41 × 10−3 | rs4648045 | T/C | 0.19 | 0.2 | 0.5 | 0.1 | 3.80 × 10−3 |
rs230529 | T/C | 0.11 | 0.1 | 0.5 | 0.3 | 2.09 × 10−7 | rs3774957 | A/T | 0.19 | 0.2 | 0.5 | 0.1 | 2.87 × 10−3 |
rs230528 | G/T | 0.06 | 0.2 | 0.5 | 0.3 | 1.60 × 10−8 | rs1287 | G/A | 0.03 | 0.2 | 0.5 | 0.2 | 5.88 × 10−8 |
rs230527 | A/G | 0.22 | 0.2 | 0.5 | 0.4 | 6.11 × 10−6 | rs7692606 | T/C | 0.19 | 0.2 | 0.5 | 0.1 | 2.81 × 10−3 |
rs230526 | A/G | 0.22 | 0.1 | 0.5 | 0.3 | 7.88 × 10−5 | rs230546 | G/C | 0 | 0.8 | 0 | 1 | 1.00 × 10−3 |
rs230525 | G/A | 0.19 | 0.3 | 0.5 | 0.4 | 3.08 × 10−5 | rs647417 | A/T | 0 | 0.8 | 0 | 1 | 8.16 × 10−5 |
rs79651301 | G/A | 0.17 | 0 | 0.3 | 0.1 | 3.11 × 10−2 | rs647424 | G/T | 0 | 0.6 | 0 | 1 | 3.50 × 10−8 |
rs4648004 | A/G | 0.22 | 0 | 0.4 | 0.1 | 6.08 × 10−3 | rs1020759 | C/T | 0 | 0 | 0.5 | 0.2 | 0.00 × 100 |
rs230523 | C/T | 0 | 0.1 | 0.5 | 0.4 | 0.00 × 100 | rs3774959 | G/A | 0.11 | 0.1 | 0.5 | 0.1 | 4.48 × 10−5 |
rs230522 | A/G | 0.11 | 0.3 | 0.5 | 0.4 | 5.24 × 10−7 | rs3774960 | C/T | 0.25 | 0.3 | 0.5 | 0.2 | 2.31 × 10−2 |
rs118882 | T/C | 0.11 | 0.3 | 0.5 | 0.4 | 1.23 × 10−6 | rs4698858 | C/G | 0.28 | 0.2 | 0.5 | 0.2 | 3.62 × 10−2 |
rs230521 | C/G | 0.19 | 0.2 | 0.5 | 0.3 | 6.59 × 10−5 | rs7684888 | G/A | 0.03 | 0.1 | 0.4 | 0.1 | 2.34 × 10−5 |
rs230520 | G/A | 0.22 | 0.3 | 0.5 | 0.4 | 6.27 × 10−4 | rs11722146 | G/A | 0.11 | 0.1 | 0.4 | 0.1 | 3.24 × 10−3 |
rs230519 | T/C | 0.22 | 0.3 | 0.5 | 0.4 | 6.10 × 10−4 | rs12509403 | C/T | 0.08 | 0.1 | 0.4 | 0.1 | 7.08 × 10−4 |
rs93059 | G/A | 0.17 | 0 | 0.5 | 0.2 | 1.51 × 10−5 | rs12509517 | G/C | 0.11 | 0.1 | 0.4 | 0.1 | 3.18 × 10−3 |
rs230492 | A/G | 0.22 | 0.3 | 0.5 | 0.4 | 6.75 × 10−4 | rs3774967 | T/C | 0.14 | 0.1 | 0.4 | 0.1 | 1.04 × 10−2 |
rs230493 | A/T | 0.22 | 0.3 | 0.5 | 0.4 | 2.89 × 10−4 | rs4699031 | A/G | 0.14 | 0.1 | 0.4 | 0.1 | 1.03 × 10−2 |
rs35680095 | G/A | 0.06 | 0 | 0.2 | 0 | 3.66 × 10−2 | rs4235406 | T/C | 0.11 | 0.2 | 0.4 | 0.1 | 3.92 × 10−3 |
rs230494 | G/A | 0.25 | 0.2 | 0.5 | 0.3 | 7.03 × 10−4 | rs9790601 | A/G | 0.06 | 0.1 | 0.4 | 0.1 | 9.49 × 10−5 |
rs230495 | A/G | 0.31 | 0.2 | 0.5 | 0.3 | 5.60 × 10−3 | rs3774968 | A/G | 0.19 | 0.4 | 0.5 | 0.4 | 2.84 × 10−3 |
rs230496 | G/A | 0.39 | 0.1 | 0.5 | 0.3 | 3.16 × 10−3 |
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Mirzo, S.M.; Kumar, A.; Sharma, N.K.; Li, L.; Balshaw, R.; Plummer, F.A.; Luo, M.; Liang, B. NFκB1 Polymorphisms Are Associated with Severe Influenza A (H1N1) Virus Infection in a Canadian Population. Microorganisms 2022, 10, 1886. https://doi.org/10.3390/microorganisms10101886
Mirzo SM, Kumar A, Sharma NK, Li L, Balshaw R, Plummer FA, Luo M, Liang B. NFκB1 Polymorphisms Are Associated with Severe Influenza A (H1N1) Virus Infection in a Canadian Population. Microorganisms. 2022; 10(10):1886. https://doi.org/10.3390/microorganisms10101886
Chicago/Turabian StyleMirzo, Suhrobjon Mullo, Anand Kumar, Naresh Kumar Sharma, Lin Li, Robert Balshaw, Francis A. Plummer, Ma Luo, and Binhua Liang. 2022. "NFκB1 Polymorphisms Are Associated with Severe Influenza A (H1N1) Virus Infection in a Canadian Population" Microorganisms 10, no. 10: 1886. https://doi.org/10.3390/microorganisms10101886