Genetic analysis of chromosome 2 in type 1 diabetes: analysis of putative loci IDDM7, IDDM12, and IDDM13 and candidate genes NRAMP1 and IA-2 and the interleukin-1 gene cluster. IMDIAB Group.

Genetics of type 1 diabetes mellitus

“…16 Subsequent linkage and TDT studies have located IDDM7 to D2S152 in several populations, although some controversy exists. [139][140][141] It is important in this regard that a single peak near the D2S1391 marker, with a LOD score of 2.62, was reported in the study by Cox et al 21 Part of this region is homologous to the region of mouse chromosome 1 containing the murine T1D susceptibility locus, idd5, in the non-obese diabetic (NOD) mouse. 142,143 A number of genes have been proposed and investigated as candidate genes for the IDDM7 region.…”

“…170 There is a microsatellite marker in the 3ЈUTR of the CTLA4 sequence, and several polymorphisms have been detected at CTLA4. 39 These polymorphisms, in particular the exon 1 (49 GϾA) SNP, have been investigated by TDT analysis in several populations, 41,140,[171][172][173][174][175][176][177][178][179][180][181][182][183][184][185][186] and combined data sets from these large studies support linkage of the CTLA4 locus to T1D. 168,171,187 Interestingly, some evidence has also been produced to suggest that CTLA4 polymorphisms may influence gene expression.…”

“…Additional evidence for IDDM13 has been obtained in two other studies. 140,187 A recent study found evidence for association to T1D of the D2S1327-D2S1471 region, which spans 3.5 cM. 187 Several IDDM13 candidate genes have been investigated, including IA-2, 140 IGFBP2, 172 IGFBP5, 172 and NRAMP1 140 but no diseaseassociated mutations have been identified in these genes.…”

Atopy in children in relation to BCG vaccination and genetic polymorphisms at SLC11A1 (formerly NRAMP1) and D2S1471

“…Thus, overall our data demonstrate that stratification by BCG vaccination has unmasked a potential genetic risk factor for atopy in the region of the SLC11A1 locus on human chromosome 2q35, and point to the importance of genotype by environment interactions in determining disease susceptibility. SLC11A1 is known to control susceptibility to a range of infectious [16][17][18][19][20][21][22][23] and autoimmune [24][25][26][27][28][29][30] diseases in man. Whilst susceptibility to infection may in part be determined by the direct influence of SLC11A1 on antimicrobial activity of macrophages, it seems likely that its pleiotropic effects in regulating Th1:Th2 balance in the immune response 36,37 will contribute to both autoimmune and infectious disease susceptibility.…”

“…In mice, Slc11a1 controls response to Mycobacterium bovis BCG, as well as to a range of other intracellular macrophage pathogens (reviewed in Blackwell et al 15 ). In man, SLC11A1 has been shown to be linked or associated with both infectious [16][17][18][19][20][21][22][23] and autoimmune [24][25][26][27][28][29][30] diseases. The protein encoded by Slc11a1/SLC11A1 localizes to membranes of late endosome/lysosomes, 31,32 and is a proton/divalent cation antiporter.…”