| 1. |
|
|
| 2. |
- Ghandil, P, et al.
(författare)
-
Crohn's disease associated CARD15 (NOD2) variants are not involved in the susceptibility to type 1 diabetes
- 2005
-
Ingår i: Molecular Genetics and Metabolism. - : Elsevier BV. - 1096-7192. ; 86:3, s. 379-383
-
Tidskriftsartikel (refereegranskat)abstract
- Three variants in the caspase recruitment domain 15/nucleotide-binding oligomerization domain 2 (CARD15/NOD2) gene have been shown to be associated with Crohn's disease (CD). There is a strong support for shared genetic determinants between various autoimmune and inflammatory diseases. In particular, linkage of type 1 diabetes (T1D) and other autoimmune and inflammatory diseases has been reported on chromosome 16, encompassing the region containing the CARD15 gene. We therefore considered this gene as a good candidate for the T1D locus mapped to this region, and we tested the three CARD15 variants in the susceptibility to T I D in two independent settings: family based association analysis in Scandinavian multiplex families that we previously showed to be linked to this region, and case/control association study in a large cohort of French diabetic patients. We found no evidence for association of these variants with T1D overall, nor in subgroups of patients with or without the major risk genotypes at HLA-DRB1, at insulin (INS), or positive or negative for autoantibodies specific to other autoimmune diseases. Our results do not support a role for CD-associated CARD15 variants in the susceptibility to T1D, and suggest that another gene is responsible for the shared susceptibility between autoimmune and inflammatory diseases mapping to this region.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Concannon, P, et al.
(författare)
-
Type 1 Diabetes: Evidence for susceptibility loci from four genome-wide linkage scans in 1,435 multiplex families.
- 2005
-
Ingår i: Diabetes. - 1939-327X. ; 54, s. 2995-3001
-
Tidskriftsartikel (refereegranskat)abstract
- Type 1 diabetes is a common, multifactorial disease with strong familial clustering (genetic risk ratio [{lambda}S] ~ 15). Approximately 40% of the familial aggregation of type 1 diabetes can be attributed to allelic variation of HLA loci in the major histocompatibility complex on chromosome 6p21 (locus-specific {lambda}S ~ 3). Three other disease susceptibility loci have been clearly demonstrated based on their direct effect on risk, INS (chromosome 11p15, allelic odds ratio [OR] ~ 1.9), CTLA4 (chromosome 2q33, allelic OR ~ 1.2), and PTPN22 (chromosome 1p13, allelic OR ~ 1.7). However, a large proportion of type 1 diabetes clustering remains unexplained. We report here on a combined linkage analysis of four datasets, three previously published genome scans, and one new genome scan of 254 families, which were consolidated through an international consortium for type 1 diabetes genetic studies (www.t1dgc.org) and provided a total sample of 1,435 families with 1,636 affected sibpairs. In addition to the HLA region (nominal P = 2.0 x 10–52), nine non–HLA-linked regions showed some evidence of linkage to type 1 diabetes (nominal P < 0.01), including three at (or near) genome-wide significance (P < 0.05): 2q31-q33, 10p14-q11, and 16q22-q24. In addition, after taking into account the linkage at the 6p21 (HLA) region, there was evidence supporting linkage for the 6q21 region (empiric P < 10–4). More than 80% of the genome could be excluded as harboring type 1 diabetes susceptibility genes of modest effect ({lambda}S ≥ 1.3) that could be detected by linkage. This study represents one of the largest linkage studies ever performed for any common disease. The results demonstrate some consistency emerging for the existence of susceptibility loci on chromosomes 2q31-q33, 6q21, 10p14-q11, and 16q22-q24 but diminished support for some previously reported locations.
|
|
| 7. |
|
|
