Page 14 - L. Genetics and genomics

[L. Genetics and genomics-14]

Strong association of regulatory single nucleotide

polymorphisms (SNPs) of the IFITM3 gene with influenza

H1N1 2009 pandemic virus infection

Yong-Chan Kim¹˙², Byung-Hoon Jeong¹˙²

¹Department of Bioactive Material Sciences, Jeonbuk National University, Jeonju 54896, South Korea, ²Korea

Zoonosis Research Institute , Jeonbuk National University, Iksan 54531, South Korea

IFITM3 gene is an important host immunological effector against viral invasion for various viruses, including
influenza A viruses. Previous studies have reported that single nucleotide polymorphisms (SNPs) of the IFITM3 gene,

such as the rs12252 SNP in the splicing receptor and the rs34481144 SNP in the promoter region, play a pivotal
role in the pathogenesis of pandemic influenza A 2009 in several ethnic groups. 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. To

the best of our knowledge, this study is the first genetic report of novel H1N1 influenza 2009 pandemic-related
SNPs