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. 2009 Jan 15;18(2):358-65.
doi: 10.1093/hmg/ddn342. Epub 2008 Oct 16.

IFIH1 polymorphisms are significantly associated with type 1 diabetes and IFIH1 gene expression in peripheral blood mononuclear cells

Siyang Liu  1 , Hongjie Wang, Yulan Jin, Robert Podolsky, M V Prasad Linga Reddy, Jennifer Pedersen, Bruce Bode, John Reed, Dennis Steed, Steve Anderson, Ping Yang, Andy Muir, Leigh Steed, Diane Hopkins, Yihua Huang, Sharad Purohit, Cong-Yi Wang, Andrea K Steck, Annalisa Montemari, George Eisenbarth, Marian Rewers, Jin-Xiong She
Affiliations

IFIH1 polymorphisms are significantly associated with type 1 diabetes and IFIH1 gene expression in peripheral blood mononuclear cells

Siyang Liu et al. Hum Mol Genet. .

Abstract

Genome-wide association (GWA) studies revealed a number of single nucleotide polymorphisms (SNPs) significantly associated with type 1 diabetes (T1D). In an attempt to confirm some of these candidate associations, we genotyped 2046 Caucasian patients and 2417 normal controls from the United States for SNPs in five genomic regions. While no evidence was obtained for four genomic regions (rs2929366/NM_144715 on chromosome 3, rs9127/Q7Z4C4 on chromosome 5, rs1445898/CAPSL on chromosome 5 and rs2302188/NM_033543 on chromosome 19), we provide strong evidence for association between T1D and multiple SNPs in the IFIH1 linkage disequilibrium (LD) block on chromosome 2q. Among the 10 SNPs genotyped for the 2q region, four SNPs located within the IFIH1 gene or at the 5' region of IFIH1 showed significant association with T1D in the Georgia population [odds ratio (OR) = 1.7-1.9] with the best P-value found at SNP rs1990760 (P = 8 x 10(-8) and OR = 1.9). Several SNPs outside of the IFIH1 gene also showed significant but weaker associations. Furthermore, IFIH1 gene expression levels in peripheral blood mononuclear cells are significantly correlated with IFIH1 genotypes, and higher IFIH1 levels are found in individuals with the susceptible genotypes (P = 0.005). Thus, both genetic association and gene expression data suggest that IFIH1 is the most plausible candidate gene implicated in T1D in this LD block.

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Figures

Figure 1.
Figure 1.
Genetic association between T1D and the IFIH1 genomic region in the Georgia population. Shown are P-values, odds ratios and their 95% confidence interval (CI) estimated for the major allele homozygous genotypes (BB) using minor allele homozygous genotypes (bb) as reference. The whole region appears to be in LD. The R2 values are presented between pairs of SNPs.
Figure 2.
Figure 2.
Correlation between IFIH1 expression level and IFIH1 genotypes. Expression levels of IFIH1 are presented for the three genotypes at each of the four IFIH1 SNPs. The mean expression level was arbitrarily set to 1 for the minor allele homozygous genotype at each SNP.
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