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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_144715on chromosome 3, rs9127/Q7Z4C4on chromosome 5, rs1445898/CAPSLon chromosome 5 and rs2302188/NM_033543on chromosome 19), we provide strong evidence for association between T1D and multiple SNPs in theIFIH1linkage disequilibrium (LD) block on chromosome 2q. Among the 10 SNPs genotyped for the 2q region, four SNPs located within theIFIH1gene or at the 5′ region ofIFIH1showed significant association with T1D in the Georgia population [odds ratio (OR) = 1.7–1.9] with the bestP-value found at SNP rs1990760 (P= 8 × 10−8and OR = 1.9). Several SNPs outside of theIFIH1gene also showed significant but weaker associations. Furthermore,IFIH1gene expression levels in peripheral blood mononuclear cells are significantly correlated withIFIH1genotypes, and higherIFIH1levels are found in individuals with the susceptible genotypes (P= 0.005). Thus, both genetic association and gene expression data suggest thatIFIH1is the most plausible candidate gene implicated in T1D in this LD block.

human molecular genetics

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