Page 13 - L. Genetics and genomics
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Strong association of regulatory single nucleotide polymorphisms (SNPs) of the
IFITM3 gene with influenza H1N1 2009 pandemic virus infection
Yong-Chan Kim, Byung-Hoon Jeong
Korea Zoonosis Research Institute, Jeonbuk National University, Iksan 570-390, Republic of Korea
BK PLUS Program in Department of Bioactive Material Sciences, Jeonbuk National University, Jeonju 561-756, Republic of Korea
ABSTRACT
IFITM3 gene is an important host immunological effector against viral invasion for
various viruses, including influenza A viruses. In the present study, the purpose was
to conduct fine mapping of the IFITM3 gene and compare the genetic differences
of the IFITM3 gene between those of healthy Koreans and H1N1 2009 pandemic
influenza-infected patients. Significant differences between healthy controls and
H1N1 pandemic influenza 2009 affected patients were observed in the genotype
frequencies of 5 regulatory SNPs, c.-204G>T (P = 0.039), c.-188T>C (P < 0.0001),
c.-181T>C (P = 0.0003), c.-178A>C (P = 0.0002) and c.-175T>C (P = 0.0002), and 1
intronic SNP, c.249+450T>C (P = 0.007), in the Korean population. However, the
IFITM3 c.-23G>A (rs34481144) polymorphism was not found in the Korean
population. In addition, we found significantly different haplotype distributions of
the IFITM3 gene between those of H1N1 influenza 2009 pandemic patients and
healthy controls. Furthermore, we identified that regulatory SNP, c.-188T>C can
modulate promoter binding ability of TFII-I transcription factor. Two haplotypes of
promoter region with different distribution between H1N1 influenza 2009
pandemic patients and healthy controls showed significantly different promoter
activity.
INTRODUCTION RESULTS CONCLUSIONS
The interferon-induced transmembrane protein 3 gene In conclusion, we identified a total of 6 novel
(IFITM3) is classified as a member of the small interferon- H1N1 influenza 2009 pandemic related SNPs, 5
stimulated genes (ISGs) and plays a paramount role in regulatory SNPs, c.-204G>T, c.-188T>C, c.-181T>C,
defense against enveloped viruses, including influenza A
viruses. A previous study reported that the rs12252 SNP, c.-178A>C and c.-175T>C, and 1 intronic SNP,
which is located in the open reading frame (ORF) of the c.249+450T>C, in the Korean population. In
IFITM3 gene, impacts the splicing procedure of protein addition, we found significantly different
production, which makes a truncated form of the IFITM3 haplotype distributions of the IFITM3 gene
protein and lowers its antiviral capacity. Thus, several
studies have focused on identifying correlations between between those of H1N1 influenza 2009 pandemic
the genotype of the rs12252 SNP and susceptibility to 2009 patients and healthy controls. Furthermore, we
pandemic influenza virus infection. However, some studies found that regulatory SNP, c.-188T>C can
failed to verify the correlation, and two studies did not find modulate the binding ability of TFII-I transcription
the rs12252 SNP-induced Δ21 IFITM3 protein splicing factor and identified that haplotypes of promoter
isoform in vitro and in vivo.
In a recent study, Allen et al. identified that the rs34481144 region, which showed different distribution
SNP located in the 5’ untranslated region (UTR) of the IFITM3 between 2009 pandemic influenza infected
gene alters the binding ability of the vital transcription factor patients and healthy controls, affect transcriptional
CTCF. Due to the rs34481144 SNP genotype being located on activity of IFITM3 gene. To the best of our
a CpG, the IFITM3 promoter activity and expression level of
the IFITM3 gene are changed. In addition, the rs34481144 knowledge, this study is the first genetic report of
SNP genotype affects the transcriptional regulation of novel H1N1 influenza 2009 pandemic related SNPs.
IFITM3-neighboring genes and showed a potent association
with the clinical results of the H1N1 influenza 2009 pandemic
in three human cohorts. Another study in Portuguese and REFERENCES
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promoter binding ability of transcription factors. used in this study. Promoter type 1 consists of T allele of c.-188T>C, C allele of c.- 2018; 674:70-9.
Furthermore, we evaluated promoter activity according to 181T>C, C allele of c.-178A>C and C allele of c.-175T>C Promoter type 2 consists of C
alleles of promoter polymorphisms which showed different allele of c.-188T>C, T allele of c.-181T>C, A allele of c.-178A>C and T allele of c.-175T>C. Kim YC, Jeong MJ, Jeong BH. Strong association of
distribution between healthy controls and 2009 pandemic (F) Promoter activity of the IFITM3 gene based on two promoter types. The symbols *, **, regulatory single nucleotide polymorphisms (SNPs) of the
influenza infected patients. and *** indicate p < 0.05, p < 0.01 and p < 0.001, respectively. RLUs indicate relative IFITM3 gene with influenza H1N1 2009 pandemic virus
luciferase light unit. NC indicates negative control. infection. Cell Mol Immunol. 2019 In Press.
