التفاصيل البيبلوغرافية
| العنوان: |
Evidence of association with type 1 diabetes in the SLC11A1 gene region |
| المؤلفون: |
Yang, Jennie HM, Downes, Kate, Howson, Joanna MM, Nutland, Sarah, Stevens, Helen E, Walker, Neil M, Todd, John A |
| بيانات النشر: |
BioMed Central Ltd. |
| سنة النشر: |
2011 |
| المجموعة: |
BioMed Central |
| الوصف: |
Background Linkage and congenic strain analyses using the nonobese diabetic (NOD) mouse as a model for human type 1 autoimmune diabetes (T1D) have identified several NOD mouse Idd (insulin dependent diabetes) loci, including Slc11a1 (formerly known as Nramp1 ). Genetic variants in the orthologous region encompassing SLC11A1 in human chromosome 2q35 have been reported to be associated with various immune-related diseases including T1D. Here, we have conducted association analysis of this candidate gene region, and then investigated potential correlations between the most T1D-associated variant and RNA expression of the SLC11A1 gene and its splice isoform. Methods Nine SNPs (rs2276631, rs2279015, rs1809231, rs1059823, rs17235409 (D543N), rs17235416 (3'UTR), rs3731865 (INT4), rs7573065 (-237 C→T) 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 ≤ 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). Results Using the case-control collection, rs3731865 (INT4) was identified to be the variant most associated with T1D ( P = 1.55 × 10 -6 ). There was also some evidence of association at rs4674297 ( P = 1.57 × 10 -4 ). No evidence of disease association was obtained at any of the loci using the family collections ( P TDT ≥ 0.13). We also did not observe a correlation between rs3731865 genotypes and SLC11A1 expression overall or with splice ... |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| العلاقة: |
http://www.biomedcentral.com/1471-2350/12/59Test |
| الإتاحة: |
http://www.biomedcentral.com/1471-2350/12/59Test |
| حقوق: |
Copyright 2011 Yang et al; licensee BioMed Central Ltd. |
| رقم الانضمام: |
edsbas.A335E0F3 |
| قاعدة البيانات: |
BASE |
