scholarly journals Non-HLA type 1 diabetes genes modulate disease risk together with HLA-DQ and islet autoantibodies

2015 ◽  
Vol 16 (8) ◽  
pp. 541-551 ◽  
Author(s):  
M Maziarz ◽  
◽  
W Hagopian ◽  
J P Palmer ◽  
C B Sanjeevi ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Disease Risk ◽  
Islet Autoantibodies ◽  
Hla Dq ◽  
Hla Type

Islet autoantibodies are associated with HLA-DQ genotypes in Han Chinese patients with type 1 diabetes and their relatives

2007 ◽  
Vol 70 (5) ◽  
pp. 369-375 ◽  
Author(s):  
J.-P. Wang ◽  
Z.-G. Zhou ◽  
J. Lin ◽  
G. Huang ◽  
C. Zhang ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Han Chinese ◽  
Islet Autoantibodies ◽  
Chinese Patients ◽  
Hla Dq

scholarly journals Type 1 Diabetes

1999 ◽  
Vol 45 (8) ◽  
pp. 1331-1338 ◽  
Author(s):  
Åke Lernmark
Keyword(s):  
Type 1 Diabetes ◽  
Islet Cell ◽  
Disease Risk ◽  
Molecular Techniques ◽  
Acid Decarboxylase ◽  
Chromosome 11 ◽  
Β Cell ◽  
Hla Dq ◽  
Secondary Failure

Abstract Type 1 (insulin-dependent) diabetes occurs worldwide and can appear at any age. The genetic susceptibility is strongly associated with HLA-DQ and DR on chromosome 6, but genetic factors on other chromosomes such as the insulin gene on chromosome 11 and the cytotoxic T-lymphocyte antigen gene on chromosome 2 may modulate disease risk. Numerous studies further support the view that environmental factors are important. Gestational infections may contribute to initiation, whereas later infections may accelerate islet β-cell autoimmunity. The pathogenesis is strongly related to autoimmunity against the islet β cells. Markers of autoimmunity include autoantibodies against glutamic acid decarboxylase, insulin, and islet cell antigen-2, a tyrosine phosphatase-like protein. Molecular techniques are used to establish reproducible and precise autoantibody assays, which have been subject to worldwide standardization. The diagnostic sensitivity (40–80%) and specificity (99%) of all three autoantibodies for type 1 diabetes are high, and double or triple positivity among first-degree relatives predicts disease. Combined genetic and antibody testing improved prediction in the general population despite the transient nature of these autoantibodies. Classification of diabetes has also been improved by autoantibody testing and may be used in type 2 diabetes to predict secondary failure and insulin requirement. Islet autoantibodies do not seem to be related to late complications but rather to metabolic control, perhaps because the presence of islet cell autoantibodies marks different residual β-cell function. Combined genetic and autoantibody screening permit rational approaches to identify subjects for secondary and tertiary intervention trials.

scholarly journals HLA class I genes modulate disease risk and age at onset together with DR-DQ in Chinese patients with insulin-requiring type 1 diabetes

Diabetologia ◽  
2021 ◽  
Author(s):  
Ziyu Jiang ◽  
Wenqian Ren ◽  
Hua Liang ◽  
Jinhua Yan ◽  
Daizhi Yang ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Disease Risk ◽  
Hla Class I ◽  
Class I ◽  
Chinese Patients ◽  
Onset Age ◽  
Disease Heterogeneity ◽  
Negatively Associated ◽  
Healthy Control

Abstract Aims/hypothesis The study aimed to investigate the effects of HLA class I genes on susceptibility to type 1 diabetes with different onset ages, in addition to the well-established effects of HLA class II genes. Methods A total of 361 patients with type 1 diabetes (192 patients with onset <18 years and 169 patients with onset ≥18 years) and 500 healthy control participants from China were enrolled and genotyped for the HLA-A, -B, -C, -DQA1, -DQB1 and -DRB1 genes using next-generation sequencing. Results The susceptible DR3 (β = −0.09, p = 0.0009) and DR4-DQ8 (β = −0.13, p = 0.0059) haplotypes were negatively associated with onset age, while the protective DR11 (β = 0.21, p = 0.0314) and DR12 (β = 0.27, p < 0.0001) haplotypes were positively associated with onset age. After adjustment for linkage disequilibrium with DR-DQ haplotypes, A*11:01:01 was positively associated with onset age (β = 0.06, p = 0.0370), while the susceptible C*15:02:01 was negatively associated with onset age (β = −0.21, p = 0.0050). The unit for β was double square-root (fourth root) transformed years of change in onset age associated with per copy of the HLA haplotype/allele. In addition, B*46:01:01 was protective (OR 0.41, 0.46; pc [corrected for multiple comparisons] = 0.0044, 0.0040), whereas A*24:02:01 (OR 2.71, 2.25; pc = 0.0003, 0.0002) and B*54:01:01 (OR 3.96, 3.79; pc = 0.0018, 0.0004) were predisposing in both the <18 group and the ≥18 group compared with healthy control participants. In the context of DR4-DQ4, A*11:01:01 (61.29% vs 28.26%, pc = 0.0144) was increased while the predisposing A*24:02:01 (19.35% vs 47.83%, pc = 0.0403) was decreased in patients with onset ≥18 years when compared with patients with onset <18 years. Conclusions/interpretation In addition to DR-DQ haplotypes, novel HLA class I alleles were detected to play a role in susceptibility to type 1 diabetes with different onset ages, which could improve the understanding of disease heterogeneity and has implications for the design of future studies. Graphical abstract

scholarly journals Next-Generation Sequencing Reveals ThatHLA-DRB3,-DRB4, and-DRB5May Be Associated With Islet Autoantibodies and Risk for Childhood Type 1 Diabetes

Diabetes ◽  
2016 ◽  
Vol 65 (3) ◽  
pp. 710-718 ◽  
Author(s):  
Lue Ping Zhao ◽  
Shehab Alshiekh ◽  
Michael Zhao ◽  
Annelie Carlsson ◽  
Helena Elding Larsson ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Next Generation Sequencing ◽  
Islet Autoantibodies ◽  
Next Generation ◽  
Childhood Type 1 Diabetes ◽  
Childhood Type ◽  
Generation Sequencing

Screening of coeliac disease in north Italian children with type 1 diabetes: limited usefulness of HLA-DQ typing

2004 ◽  
Vol 93 (5) ◽  
pp. 628-632 ◽  
Author(s):  
G Contreas ◽  
E Valletta ◽  
D Ulmi ◽  
S Cantoni ◽  
L Pinelli
Keyword(s):  
Type 1 Diabetes ◽  
Coeliac Disease ◽  
Hla Dq ◽  
Italian Children ◽  
Limited Usefulness

Discordant association of islet autoantibodies with high-risk HLA genes in Chinese type 1 diabetes

2011 ◽  
Vol 27 (8) ◽  
pp. 899-905 ◽  
Author(s):  
Yong Gu ◽  
Mei Zhang ◽  
Heng Chen ◽  
Zhixiao Wang ◽  
Chunyan Xing ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
High Risk ◽  
Islet Autoantibodies ◽  
Hla Genes

scholarly journals The role of coronary artery calcification testing in incident coronary artery disease risk prediction in type 1 diabetes

Diabetologia ◽  
2018 ◽  
Vol 62 (2) ◽  
pp. 259-268 ◽  
Author(s):  
Jingchuan Guo ◽  
Sebhat A. Erqou ◽  
Rachel G. Miller ◽  
Daniel Edmundowicz ◽  
Trevor J. Orchard ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Type 1 Diabetes ◽  
Coronary Artery ◽  
Risk Prediction ◽  
Coronary Artery Calcification ◽  
Disease Risk ◽  
Coronary Artery Disease Risk ◽  
Artery Disease
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