Molecular aspects of type 1 diabetes

Kelly, M. A.; Ml, Rayner; Mijovic, C.; Barnett, Anthony

doi:10.1136/mp.56.1.1

Cited by 77 publications

(67 citation statements)

References 109 publications

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“…Approximately, 50% of the genetic susceptibility to T1D is explained by four established genetic risk factors, including human leukocyte antigen class II genes, the insulin gene, cytotoxic T-lymphocyteassociated antigen 4 (CTLA4) and protein tyrosine phosphatase PTPN22. [2][3][4] These findings indicate that analyzing candidate genes is a fruitful approach in the search for T1D susceptibility genes, but that other genetic risk factors still need to be identified.…”

Section: Introductionmentioning

confidence: 99%

Genetic variants of RANTES are associated with serum RANTES level and protection for type 1 diabetes

et al. 2006

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RANTES (regulated on activation, normal T-cell expressed and secreted) is a T-helper type 1 (Th1) chemokine that promotes T-cell activation and proliferation. RANTES is genetically associated with asthma, sarcoidosis and multiple sclerosis. The concentration of RANTES is increased at inflammation sites in different autoimmune diseases. Type 1 diabetes (T1D) is a Th1-mediated disease with complex genetic predisposition. We tested RANTES as a candidate gene for association with T1D using three single-nucleotide polymorphism (SNP) variants (rs4251719, rs2306630 and rs2107538) to capture haplotype information. The minor alleles of all SNPs were transmitted less frequently to T1D offspring (transmission rates 37.3% (P ¼ 0.002), 38.7% (P ¼ 0.007) and 41.0% (P ¼ 0.01)) and were less frequently present in patients compared to controls (P ¼ 0.009, 0.03 and 0.04, respectively). A similar protective effect was observed for the haplotype carrying three minor alleles (transmission disequilibrium test (TDT): P ¼ 0.003; odds ratio (OR) ¼ 0.55; confidence interval (CI): 0.37-0.83; case/control: P ¼ 0.03; OR ¼ 0.74; CI: 0.55-0.98). Both patients and controls carrying the protective haplotype express significantly lower serum levels of RANTES compared to non-carriers. Subsequently, we tested a cohort of 310 celiac disease patients, but failed to detect association. RANTES SNPs are significantly associated with RANTES serum concentration and development of T1D. The rs4251719*A-rs2306630*A-rs2107538*A haplotype associated with low RANTES production confers protection from T1D. Our data imply that RANTES is associated with T1D both genetically and functionally, and contributes to diabetesprone Th1 cytokine profile.

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Section: Introductionmentioning

confidence: 99%

Genetic variants of RANTES are associated with serum RANTES level and protection for type 1 diabetes

et al. 2006

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“…The HLA shows association with T1D (locus termed IDDM1; Table 1) [15][16][17][18][19][20][21][22] and accounts for approximately 40% of the familial aggregation of the disease. The predisposing HLA class II haplotypes, HLA-DRB1*04, DQB1*03:02 (identified by serology as DR4) and DRB1*03:01, DQB1*02:01 (DR3) are present in 95% of affected individuals.…”

Section: Familial Risk Of Type 1 Diabetesmentioning

confidence: 99%

From Markers to Molecular Mechanisms: Type 1 Diabetes in the Post-GWAS Era

Baxter

Jordan²

2012

Rev Diabet Stud

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■ AbstractBy the year 2000, a draft of the human genome sequence was completed. Millions of single-nucleotide polymorphisms (SNPs) had been deposited into public databases, and high throughput technologies were under development for SNP genotyping. At that time, it was predicted that large case control association studies would provide far better resolution and power than genome-wide linkage studies. Type 1 diabetes was one of the first phenotypes to be examined by genome-wide association studies (GWAS), and to date over 50 genomic regions have been associated with the disease.In general, the great majority of these loci individually contribute a relatively small degree of risk, and most loci lie outside of coding sequences. The identification of molecular mechanisms from these genomic data therefore remains a significant challenge. Here, we summarize genetic candidate, linkage, and association studies of type 1 diabetes and discuss a potential strategy to identify mechanisms of disease from genomic data.

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“…Type 1 Diabetes Mellitus (DM1) can result in serious complications that reduce both quality of life and life expectancy [2]. These complications include retinopathy, renal disease, atherosclerotic macrovascular disease, debilitating neuropathies and hepatic diseases, such as Hepatic Steatosis (HS).…”

Section: Introductionmentioning

confidence: 99%

Hepatic Steatosis Markers in Diabetic Rats Trained at the Aerobic/ Anaerobic Transition

2016

J Liver

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Aims: To analyze the effects of exercise performed at the aerobic/anaerobic transition (Lan) on Non-Alcoholic Hepatic Steatosis (NAHS) markers in type 1 diabetic rats.Methods: Adult Wistar rats were separated into four groups: Sedentary Control (SC), Trained Control (TC), Sedentary Diabetic (SD) and Trained Diabetic (TD). The trained groups swam supporting workloads equivalent to the Lan for one hour/day, five days/week, for eight weeks. Body weight, serum albumin concentrations, glucose concentrations, Free Fatty Acid (FFA) concentrations, NAHS markers (Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) and total lipid concentrations in the liver were analyzed. Results:The diabetic groups showed higher serum glucose concentrations and more weight loss compared to the controls, although the TD group was less affected than the SD group. Training resulted in a decrease in serum glucose levels in the diabetic rats. The NAHS markers, total lipid concentrations in the liver and serum albumin concentrations did not differ between the groups. However, the diabetic animals had higher serum FFA levels than the controls. Conclusion:Physical training at Lan attenuates weight loss and improves serum glucose homeostasis in diabetic animals. In addition, serum ALT and AST enzymes proved to be adequate markers of lipid levels in the livers in this animal model.

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Molecular aspects of type 1 diabetes

Cited by 77 publications

References 109 publications

Genetic variants of RANTES are associated with serum RANTES level and protection for type 1 diabetes

Genetic variants of RANTES are associated with serum RANTES level and protection for type 1 diabetes

From Markers to Molecular Mechanisms: Type 1 Diabetes in the Post-GWAS Era

Hepatic Steatosis Markers in Diabetic Rats Trained at the Aerobic/ Anaerobic Transition

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