%0 Journal Article
%T Evidence of association with type 1 diabetes in the SLC11A1 gene region
%A Jennie HM Yang
%A Kate Downes
%A Joanna MM Howson
%A Sarah Nutland
%A Helen E Stevens
%A Neil M Walker
%A John A Todd
%J BMC Medical Genetics
%D 2011
%I BioMed Central
%R 10.1186/1471-2350-12-59
%X Nine SNPs (rs2276631, rs2279015, rs1809231, rs1059823, rs17235409 (D543N), rs17235416 (3'UTR), rs3731865 (INT4), rs7573065 (-237 C¡úT) and rs4674297) were genotyped using TaqMan genotyping assays and the polymorphic promoter microsatellite (GT)n was genotyped using PCR and fragment length analysis. A maximum of 8,863 T1D British cases and 10,841 British controls, all of white European descent, were used to test association using logistic regression. A maximum of 5,696 T1D families were also tested for association using the transmission/disequilibrium test (TDT). We considered P ¡Ü 0.005 as evidence of association given that we tested nine variants in total. Upon identification of the most T1D-associated variant, we investigated the correlation between its genotype and SLC11A1 expression overall or with splice isoform ratio using 42 PAXgene whole blood samples from healthy donors by quantitative PCR (qPCR).Using the case-control collection, rs3731865 (INT4) was identified to be the variant most associated with T1D (P = 1.55 ¡Á 10-6). There was also some evidence of association at rs4674297 (P = 1.57 ¡Á 10-4). No evidence of disease association was obtained at any of the loci using the family collections (PTDT ¡Ý 0.13). We also did not observe a correlation between rs3731865 genotypes and SLC11A1 expression overall or with splice isoform expression.We conclude that rs3731685 (INT4) in the SLC11A1 gene may be associated with T1D susceptibility in the European ancestry population studied. We did not observe a difference in SLC11A1 expression at the RNA level based on the genotypes of rs3731865 in whole blood samples. However, a potential correlation cannot be ruled out in purified cell subsets especially monocytes or macrophages.Type 1 diabetes (T1D) is a heritable polygenic autoimmune disease in which both genetic and environmental factors contribute to pathogenesis. To date over 50 loci have been identified that affect risk of T1D [1-3]. The causal genes, variants and hapl
%U http://www.biomedcentral.com/1471-2350/12/59