Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two large population-based case-control studies are reviewed. The aim is to determine the effects of HLA, other genetic factors and immune markers (ICA, IAA and GAD65Ab) on the age at onset of insulin-dependent diabetes mellitus (IDDM) in 0-34 year olds. The primary HLA risk gene sequence for IDDM was difficult to identify because of the low recombination frequency within the HLA region. The frequency of the DR3-DQA1*0501-DQB1*0201 haplotype and the DR3-DQA1*0501-DQB1*0201 (DQ2)/DR4-DQA1*0301-DQB1*0302 (DQ8) genotype were higher among patients diagnosed before the age of 10 compared with those diagnosed after the age of 30. The negatively associated haplotype, DR15-DQA1*0102-DQB1*0602 was absent before the age of 10, but the frequency increased with increasing age at onset. The IDDM2 gene representing the variable number of tandem repeat (VNTR) sequences and 5' of the insulin gene on chromosome 11 were associated with IDDM since homozygous short VNTR was positive but not homozygous, and heterozygous long VNTR was negatively associated with the disease. The diagnostic sensitivity and specificity of GAD65 (GA65Ab) and insulin (IAA) autoantibodies varied with the age at onset and gender. GAD65Ab had the highest sensitivity (> 80%) in patients older than 20 years of age with no difference in gender. The lowest sensitivity (54%) was in 0-10 year old boys, while age did not affect the sensitivity in girls. In contrast, the sensitivity of IAA was highest (46%) before the age of 15 but decreased thereafter as did the sensitivity for ICA. Classification of patients who develop IDDM above 20-25 years of age was inadequate since many patients classified with NIDDM either had GAD65Ab or ICA or developed these antibodies after 1-2 years of NIDDM. We conclude that not only age but also gender affect the risk for IDDM associated with HLA, other IDDM genes as well as commonly used immunological markers for IDDM.
 ...
PMID:Genetic and immunological findings in patients with newly diagnosed insulin-dependent diabetes mellitus. The Swedish Childhood Diabetes Study Group and The Diabetes Incidence in Sweden Study (DISS) Group. 885 82

We review the strategy used to identify a susceptibility locus (IDDM2) for type 1 (insulin dependent) diabetes mellitus. As type 1 diabetes is becoming the paradigm for dissecting multifactorial disease genetics, the approach described provides important general guidelines for positional cloning of human disease polygenes. Main topics include: (a) historical conspectus of the mapping and identification of IDDM2--a critical survey of the work leading up to the conclusion that IDDM2 most likely corresponds to allelic variation at the insulin gene minisatellite (VNTR) locus; (b) the nature of allelic (length and sequence) variation at the VNTR locus; (c) gene interactions and disease pathogenesis; (d) mechanism of action of the INS VNTR in type 1 diabetes--insulin gene expression, parent-of-origin effects (genomic imprinting); and (e) summary and future prospects--alleles of the insulin VNTR that are protective for type 1 diabetes appear to encode susceptibility to type 2 diabetes.
 ...
PMID:Human type 1 diabetes and the insulin gene: principles of mapping polygenes. 898 58