Fig. 1.

Polymorphisms of the interferon-induced transmembrane protein 3 gene (IFITM3). a Gene map of and polymorphisms identified in the human interferon-induced transmembrane protein 3 gene (IFITM3) on chromosome 11. The open reading frame (ORF) within the exons is indicated by shaded blocks, and the 5′ and 3′ untranslated regions (UTRs) are indicated by white blocks. Edged horizontal bars indicate the regions sequenced. Arrows indicate the polymorphisms found in this study. Asterisks denote novel single nucleotide polymorphisms (SNPs). b Electropherogram of novel SNPs of the human IFITM3 gene. A novel SNP, c.249 + 74G > T, was identified in this study. The four colors indicate individual bases of the DNA sequence using an ABI 3730 automatic sequencer (blue: cytosine, red: thymine, black: guanine, green: adenine). The upper panel indicates a guanine homozygote for c.249 + 74G > T, and the lower panel indicates a guanine/thymine heterozygote for c.249 + 74G > T. c Comparison of the genotype and allele distributions in 4 regulatory SNPs of the IFITM3 gene, which are strongly associated with the susceptibility of influenza H1N1 2009 pandemic infection. d Analysis of the binding ability of transcription factors among 4 haplotypes of proximal promoter sequences of the human IFITM3 gene. The red box indicates the difference in transcription binding between haplotypes 1 and 2 and haplotypes 3 and 4. The Y-shaped bar indicates a zoomed-in area of the c-188T > C region, which showed differences in TFII-I binding between haplotypes 1 and 2 and haplotypes 3 and 4. e Schematic map of functional promoter segments of the IFITM3 gene used in this study. Promoter type 1 consists of the T allele of c.−188T > C, the C allele of c.−181T > C, the C allele of c.−178A > C and the C allele of c.−175T > C. Promoter type 2 consists of the C allele of c.−188T > C, the T allele of c.−181T > C, the A allele of c.−178A > C and the T allele of c.−175T > C. f Promoter activity of the IFITM3 gene based on two promoter types. The symbols *, **, and *** indicate p < 0.05, p < 0.01 and p < 0.001, respectively. RLUs indicate the relative luciferase light unit. NC indicates a negative control