Journal Article

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

Siyang Liu, Hongjie Wang, Yulan Jin, Robert Podolsky, MV 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 and Jin-Xiong She

in Human Molecular Genetics

Volume 18, issue 2, pages 358-365
Published in print January 2009 | ISSN: 0964-6906
Published online October 2008 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddn342
IFIH1 polymorphisms are significantly associated with type 1 diabetes and IFIH1 gene expression in peripheral blood mononuclear cells

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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 × 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.

Journal Article.  5503 words.  Illustrated.

Subjects: Genetics and Genomics

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