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TYPE 1 DIABETES MELLITUS 10; T1D10

TYPE 1 DIABETES MELLITUS 10; T1D10

Alternative titles; symbolsDIABETES MELLITUS, INSULIN-DEPENDENT, 10; IDDM10INSULIN-DEPENDENT DIABETES MELLITUS 10One of the regions identified in a type 1 diabet...

Alternative titles; symbols

  • DIABETES MELLITUS, INSULIN-DEPENDENT, 10; IDDM10
  • INSULIN-DEPENDENT DIABETES MELLITUS 10

One of the regions identified in a type 1 diabetes (see 222100) genomewide linkage scan extended from D10S197 to D10S220 across the centromere of chromosome 10 (Davies et al., 1994). Reed et al. (1997) undertook large scale, high resolution, multipoint affected sib pair linkage and single point transmission disequilibrium test (TDT) linkage analyses of 10p11-q11 in U.K., U.S., Norwegian, Sardinian, and Italian type 1 diabetic Caucasian populations. Linkage to 2 markers in this region was indicated by TDT. An allele at D10S588 was positively associated in a U.K. case-control study and was neutrally transmitted in CEPH families.

By using a haplotype tag SNP approach, Vella et al. (2005) tested type 1 diabetes sample collections consisting of 7,457 cases and controls and of 725 multiplex families. Tag SNPs were analyzed using a multilocus test to provide a regional test for association. They found strong statistical evidence in the case-control collection for a type 1 diabetes locus in the CD25 (IL2RA; 147730) region of chromosome 10p15 and replicated the association in the family collection. Vella et al. (2005) recognized that association might not be with CD25 itself, but rather with a causal variant in linkage disequilibrium with CD25.

In an analysis of up to 5,312 individuals with type 1 diabetes and 6,855 controls, Lowe et al. (2007) localized the type 1 diabetes association in the IL2RA gene region to 2 independent groups of SNPs, spanning overlapping regions of 14 and 40 kb, encompassing IL2RA intron 1 and the 5-prime regions of IL2RA and flanking gene RBM17 (606935) (odds ratio = 2.04; p = 10(-28)). IL2RA type 1 diabetes susceptibility genotypes (see, e.g., 147730.0002-147730.0003) were associated with lower circulating levels of soluble IL2RA (p = 6.28 x 10(-28)), suggesting that an inherited lower immune responsiveness predisposes to type 1 diabetes.

Tags: 10p15.1