IFIH1 polymorphisms are significantly associated with type 1 diabetes and IFIH1 gene expression in peripheral blood mononuclear cells
Open Access
- 16 October 2008
- journal article
- research article
- Published by Oxford University Press (OUP) in Human Molecular Genetics
- Vol. 18 (2), 358-365
- https://doi.org/10.1093/hmg/ddn342
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 × 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.Keywords
This publication has 25 references indexed in Scilit:
- IFIH1-GCA-KCNH7 locus: influence on multiple sclerosis riskEuropean Journal of Human Genetics, 2008
- TLR-mediated induction of negative regulatory ligands on dendritic cellsJournal of Molecular Medicine, 2008
- Genome Wide Association (GWA) Study for Early Onset Extreme Obesity Supports the Role of Fat Mass and Obesity Associated Gene (FTO) VariantsPLOS ONE, 2007
- The association between the IFIH1 locus and type 1 diabetesDiabetologia, 2007
- The A946T polymorphism in the interferon induced helicase gene does not confer susceptibility to Graves’ disease in Chinese populationEndocrine, 2007
- A genome-wide association study of nonsynonymous SNPs identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) regionNature Genetics, 2006
- Genetic Association Between a Lymphoid Tyrosine Phosphatase (PTPN22) and Type 1 DiabetesDiabetes, 2005
- Replication of an Association Between the Lymphoid Tyrosine Phosphatase Locus (LYP/PTPN22) With Type 1 Diabetes, and Evidence for Its Role as a General Autoimmunity LocusDiabetes, 2004
- Genetic Association of the R620W Polymorphism of Protein Tyrosine Phosphatase PTPN22 with Human SLEAmerican Journal of Human Genetics, 2004
- A Missense Single-Nucleotide Polymorphism in a Gene Encoding a Protein Tyrosine Phosphatase (PTPN22) Is Associated with Rheumatoid ArthritisAmerican Journal of Human Genetics, 2004