Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Type 1 diabetes (T1D) is a genetically complex disorder of glucose homeostasis that results from the autoimmune destruction of the insulin-secreting cells of the pancreas. Two previous whole-genome scans for linkage to T1D in 187 and 356 families containing affected sib pairs (ASPs) yielded apparently conflicting results, despite partial overlap in the families analyzed. However, each of these studies individually lacked power to detect loci with locus-specific disease prevalence/sib-risk ratios (lambda(s)) <1.4. In the present study, a third genome scan was performed using a new collection of 225 multiplex families with T1D, and the data from all three of these genome scans were merged and analyzed jointly. The combined sample of 831 ASPs, all with both parents genotyped, provided 90% power to detect linkage for loci with lambda(s) = 1.3 at P=7.4x10(-4). Three chromosome regions were identified that showed significant evidence of linkage (P<2.2x10(-5); LOD scores >4), 6p21 (IDDM1), 11p15 (IDDM2), 16q22-q24, and four more that showed suggestive evidence (P<7.4x10(-4), LOD scores > or =2.2), 10p11 (IDDM10), 2q31 (IDDM7, IDDM12, and IDDM13), 6q21 (IDDM15), and 1q42. Exploratory analyses, taking into account the presence of specific high-risk HLA genotypes or affected sibs' ages at disease onset, provided evidence of linkage at several additional sites, including the putative IDDM8 locus on chromosome 6q27. Our results indicate that much of the difficulty in mapping T1D susceptibility genes results from inadequate sample sizes, and the results point to the value of future international collaborations to assemble and analyze much larger data sets for linkage in complex diseases.
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PMID:Seven regions of the genome show evidence of linkage to type 1 diabetes in a consensus analysis of 767 multiplex families. 1150 94

IDDM10 on chromosome 10p11-q11 has been identified as a putative diabetes susceptibility locus through affected sib-pair (ASP) linkage analysis in UK nuclear families [Davies et al., 1994: Nature 371:130-136; Reed et al., 1997: Hum Mol Genet 6:1011-1016; Mein et al., 1998: Nat Genet 19:297-300]. We extended analysis of linkage to type 1 diabetes in this region by typing a total of 61 markers in a maximum of 418 UK sib-pairs (UK418; peak MLS = 3.84). We then stratified the dataset based on analyses performed previously by both our group [Mein et al., 1998: Nat Genet 19:297-300] and others [Paterson et al., 1999: Hum Hered 49:197-204; Paterson and Petronis, 1999a: Am J Med Genet 84:15-19; Paterson and Petronis, 2000a: J Med Genet 37:186-191; Paterson and Petronis, b: Eur J Hum Genet 8:145-148] and used a permutation procedure to assess the significance of the results. We conclude that the results obtained had a high probability of occurring by chance alone. These data highlight the limitations of stratifying small datasets (n < 500) by additional criteria and the recurrent problems of multiple testing in genetic analysis.
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PMID:Limitations of stratifying sib-pair data in common disease linkage studies: an example using chromosome 10p14-10q11 in type 1 diabetes. 1240 6

Stromal-cell derived factor-1 (SDF-1) is a powerful chemokine that upregulates T-cell migration and activation. The gene for SDF-1 is located near type 1 diabetes susceptibility locus IDDM10, suggesting a contribution by SDF-1 to the induction of diabetes. Recently the role of SDF-1 gene polymorphism in the clinical presentation of type 1 diabetes in French population has been reported. To test the putative involvement of SDF-1 gene polymorphism in predisposition to or clinical heterogeneity of type 1 diabetes in Japanese population, we conducted the case-control study. The SDF1-3'A variant (801 G to A in the 3'-untranslated region) was determined by the polymerase chain reaction-restriction fragment length polymorphism technique in 184 patients with abrupt-onset type 1 diabetes and 106 healthy control subjects. No significant difference in allele and genotype frequencies of SDF1-3'A variant was found between type 1 diabetic patients and healthy controls. However, the SDF1-3'A variant was strongly associated with early-onset diabetes in a recessive model (AA versus AG + GG, p = 0.017). The mean age-at-onset in patients carrying SDF1-3'AA genotype was significantly younger than that in patients with SDF1-3' AG or GG genotype (p = 0.028). The frequencies of SDF1-3' A variant were significantly increased in HLA-DR4/9 patients compared with non-DR4/9 patients (p = 0.008). These results suggest that the SDF-1 gene polymorphism is associated with the age-at-onset of type 1 diabetes in Japanese population.
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PMID:Stromal-cell derived factor-1 chemokine gene variant is associated with type 1 diabetes age at onset in Japanese population. 1452 95

Type 1 diabetes is a heterogenous autoimmune disease and is frequently associated with other organ-specific autoimmune diseases, including autoimmune thyroid disease (AITD). Type 1 diabetic patients with AITD are known to have clinical and immunological features distinct from patients without AITD. This study investigated whether stromal cell-derived factor (SDF)-1 gene polymorphism is associated with susceptibility to type 1 diabetes and AITD. SDF-1 is a powerful chemokine that upregulates T-cell migration and activation, and the gene for SDF-1 is located near type 1 diabetes susceptibility locus IDDM10. The SDF1-3'A variant (801 G to A in the 3'-untranslated region) was determined by the PCR-RFLP technique in 54 type 1 diabetic patients with AITD, 75 type 1 diabetic patients without AITD, 137 nondiabetic patients with AITD, and 106 healthy subjects in a case-control study. No significant differences on the allele and genotype frequencies of the SDF1 gene polymorphism were found, not only in type 1 diabetic patients with AITD compared with normal controls but also between nondiabetic patients with AITD and healthy control subjects. These results suggest that the SDF1-3'A variant is not associated with genetic susceptibility to type 1 diabetic patients and AITD.
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PMID:Stromal cell-derived factor-1 chemokine gene variant in patients with type 1 diabetes and autoimmune thyroid disease. 1569 97