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Genetic variants in IL1A and IL1B contribute to the susceptibility to 2009 pandemic H1N1 influenza A virus.

Liu Y, Li S, Zhang G, Nie G, Meng Z, Mao D, Chen C, Chen X, Zhou B, Zeng G - BMC Immunol. (2013)

Bottom Line: The polymorphisms of rs17561 in IL1A gene and rs1143627 in IL1B gene were found to be associated with susceptibility to A(H1N1)pdm09 with P values of 0.003 (OR 2.08, 95% CI 1.27-3.41) and 0.002 (OR 1.62 , 95% CI 1.20-2.18), respectively.However, no significant difference in allelic frequency was observed for other SNPs between cases and controls.This study provides a new insight into pathogenesis of A(H1N1)pdm09, suggesting that genetic variants of IL-1A and IL-1B may exert a substantial impact on the susceptibility of A(H1N1)pdm09 virus infection.

View Article: PubMed Central - HTML - PubMed

Affiliation: Guangdong Key Laboratory for Emerging Infectious Diseases, Shenzhen Third People’s Hospital, Guangdong Medical College, Shenzhen, China.

ABSTRACT

Background: Host genetic variations may contribute to disease susceptibility of influenza. IL-1A and IL-1B are important inflammatory cytokines that mediate the inflammation and initiate the immune response against virus infection. In this study, we investigated the relationship between single-nucleotide polymorphisms (SNPs) of Interleukin-1A (IL-1A) and Interleukin-1B (IL-1B) and the susceptibility to 2009 pandemic A/H1N1 influenza (A(H1N1)pdm09). 167 patients whom were confirmed with A(H1N1)pdm09 and 192 healthy controls were included in this study. Four SNPs (rs1304037, rs16347, rs17561, rs2071373) in IL1A gene and three SNPs (rs1143623, rs3917345, rs1143627) in IL1B gene were genotyped by using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry platform, and the associations of the genetic variants of IL-1 with susceptibility to A(H1N1)pdm09 were then assessed.

Results: The polymorphisms of rs17561 in IL1A gene and rs1143627 in IL1B gene were found to be associated with susceptibility to A(H1N1)pdm09 with P values of 0.003 (OR 2.08, 95% CI 1.27-3.41) and 0.002 (OR 1.62 , 95% CI 1.20-2.18), respectively. However, no significant difference in allelic frequency was observed for other SNPs between cases and controls.

Conclusions: This study provides a new insight into pathogenesis of A(H1N1)pdm09, suggesting that genetic variants of IL-1A and IL-1B may exert a substantial impact on the susceptibility of A(H1N1)pdm09 virus infection.

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Related in: MedlinePlus

MALDI–TOF mass spectrum–based analysis of rs17561 and rs1143627 SNPs. Typical MALDI-TOF MS spectra from three DNA samples are shown. Dashed lines mark the unextended primers and product/extended primers. Rs17561 SNP includes GG, GT, and TT genotypes, and rs1143627 SNP includes CC, TC, and TT genotypes.
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Figure 2: MALDI–TOF mass spectrum–based analysis of rs17561 and rs1143627 SNPs. Typical MALDI-TOF MS spectra from three DNA samples are shown. Dashed lines mark the unextended primers and product/extended primers. Rs17561 SNP includes GG, GT, and TT genotypes, and rs1143627 SNP includes CC, TC, and TT genotypes.

Mentions: To choose relevant SNPs for IL1A and IL1B gene, we considered about 100 known and rare variants, which are publicly available in database (dbSNP: http://www.ncbi.nlm.nih.gov/SNP/; CYPallele nomenclature: http://www.cypalleles.ki.se). After bioinformatic analysis and prediction for SNPs that may influence gene expression or protein structure and function, a total of 7 SNPs, including 4 in the IL1A gene (rs17561 G > T, rs1304037 A > G, rs2071373 C > T, rs16347 DEL > TGAA), and 3 in the IL1B gene (rs1143623 G > C, rs3917345 DEL > TGGT, rs1143627 T > C), were selected finally. The locations of these SNPs in IL-1 were shown in Figure 1. Rs2071373 is in the intron 3 and 209 bp after the extron 3 (the length from the coding sequence start site to the extron 3 is 96 bp) of IL1A gene. Rs17561 is in the extron 5 of IL1A gene and 340 bp after coding sequence (CDS) start site. Rs1304037 is in the 3′UTR of IL1A gene and 408 bp after CDS terminal site. Rs16347 is in the 3′UTR of IL1A gene, 922 bp after CDS terminal site and a 4 bp fraction is missing. 3 SNPs of IL1B gene are all in the promoter region. Rs1143623 is 1473 bp before the transcription start site of IL1B gene. Rs3917345 is 798 bp before the transcription start site of IL1B gene and a 4 bp fraction is missing. Rs1143627 is 31 bp before the transcription start site of IL1B gene. Genotypes of these 7 SNPs were determined using the MALDI-TOF mass spectrometry platform in a cohort of 167 cases and 192 controls. The intensities of mass signal of rs17561 and rs1143627 SNPs from three DNA samples analyzed by MALDI-TOF mass spectrum were shown in Figure 2.


Genetic variants in IL1A and IL1B contribute to the susceptibility to 2009 pandemic H1N1 influenza A virus.

Liu Y, Li S, Zhang G, Nie G, Meng Z, Mao D, Chen C, Chen X, Zhou B, Zeng G - BMC Immunol. (2013)

MALDI–TOF mass spectrum–based analysis of rs17561 and rs1143627 SNPs. Typical MALDI-TOF MS spectra from three DNA samples are shown. Dashed lines mark the unextended primers and product/extended primers. Rs17561 SNP includes GG, GT, and TT genotypes, and rs1143627 SNP includes CC, TC, and TT genotypes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750637&req=5

Figure 2: MALDI–TOF mass spectrum–based analysis of rs17561 and rs1143627 SNPs. Typical MALDI-TOF MS spectra from three DNA samples are shown. Dashed lines mark the unextended primers and product/extended primers. Rs17561 SNP includes GG, GT, and TT genotypes, and rs1143627 SNP includes CC, TC, and TT genotypes.
Mentions: To choose relevant SNPs for IL1A and IL1B gene, we considered about 100 known and rare variants, which are publicly available in database (dbSNP: http://www.ncbi.nlm.nih.gov/SNP/; CYPallele nomenclature: http://www.cypalleles.ki.se). After bioinformatic analysis and prediction for SNPs that may influence gene expression or protein structure and function, a total of 7 SNPs, including 4 in the IL1A gene (rs17561 G > T, rs1304037 A > G, rs2071373 C > T, rs16347 DEL > TGAA), and 3 in the IL1B gene (rs1143623 G > C, rs3917345 DEL > TGGT, rs1143627 T > C), were selected finally. The locations of these SNPs in IL-1 were shown in Figure 1. Rs2071373 is in the intron 3 and 209 bp after the extron 3 (the length from the coding sequence start site to the extron 3 is 96 bp) of IL1A gene. Rs17561 is in the extron 5 of IL1A gene and 340 bp after coding sequence (CDS) start site. Rs1304037 is in the 3′UTR of IL1A gene and 408 bp after CDS terminal site. Rs16347 is in the 3′UTR of IL1A gene, 922 bp after CDS terminal site and a 4 bp fraction is missing. 3 SNPs of IL1B gene are all in the promoter region. Rs1143623 is 1473 bp before the transcription start site of IL1B gene. Rs3917345 is 798 bp before the transcription start site of IL1B gene and a 4 bp fraction is missing. Rs1143627 is 31 bp before the transcription start site of IL1B gene. Genotypes of these 7 SNPs were determined using the MALDI-TOF mass spectrometry platform in a cohort of 167 cases and 192 controls. The intensities of mass signal of rs17561 and rs1143627 SNPs from three DNA samples analyzed by MALDI-TOF mass spectrum were shown in Figure 2.

Bottom Line: The polymorphisms of rs17561 in IL1A gene and rs1143627 in IL1B gene were found to be associated with susceptibility to A(H1N1)pdm09 with P values of 0.003 (OR 2.08, 95% CI 1.27-3.41) and 0.002 (OR 1.62 , 95% CI 1.20-2.18), respectively.However, no significant difference in allelic frequency was observed for other SNPs between cases and controls.This study provides a new insight into pathogenesis of A(H1N1)pdm09, suggesting that genetic variants of IL-1A and IL-1B may exert a substantial impact on the susceptibility of A(H1N1)pdm09 virus infection.

View Article: PubMed Central - HTML - PubMed

Affiliation: Guangdong Key Laboratory for Emerging Infectious Diseases, Shenzhen Third People’s Hospital, Guangdong Medical College, Shenzhen, China.

ABSTRACT

Background: Host genetic variations may contribute to disease susceptibility of influenza. IL-1A and IL-1B are important inflammatory cytokines that mediate the inflammation and initiate the immune response against virus infection. In this study, we investigated the relationship between single-nucleotide polymorphisms (SNPs) of Interleukin-1A (IL-1A) and Interleukin-1B (IL-1B) and the susceptibility to 2009 pandemic A/H1N1 influenza (A(H1N1)pdm09). 167 patients whom were confirmed with A(H1N1)pdm09 and 192 healthy controls were included in this study. Four SNPs (rs1304037, rs16347, rs17561, rs2071373) in IL1A gene and three SNPs (rs1143623, rs3917345, rs1143627) in IL1B gene were genotyped by using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry platform, and the associations of the genetic variants of IL-1 with susceptibility to A(H1N1)pdm09 were then assessed.

Results: The polymorphisms of rs17561 in IL1A gene and rs1143627 in IL1B gene were found to be associated with susceptibility to A(H1N1)pdm09 with P values of 0.003 (OR 2.08, 95% CI 1.27-3.41) and 0.002 (OR 1.62 , 95% CI 1.20-2.18), respectively. However, no significant difference in allelic frequency was observed for other SNPs between cases and controls.

Conclusions: This study provides a new insight into pathogenesis of A(H1N1)pdm09, suggesting that genetic variants of IL-1A and IL-1B may exert a substantial impact on the susceptibility of A(H1N1)pdm09 virus infection.

Show MeSH
Related in: MedlinePlus