Sequencing of the Second Exon of the MHC Class II DQ6 Alleles in Patients with Type 1 Diabetes

Ml, Rayner; Ma, Kelly; Mijovic, C.; Ah, Barnett

doi:10.1080/08916930290016637

Cited by 7 publications

(6 citation statements)

References 9 publications

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“…It has been considered that DQB1*0602 has a natural protective effect against Type 1A diabetes and that it can even prevent progression to overt diabetes in ICA‐positive relatives of patients with Type 1A diabetes 22 . However, some new‐onset patients in the present study carried the DQB1*0602 allele and were positive for anti‐islet autoantibodies; this has been observed in other studies, suggesting the protective effect associated with DQ*0602 is not absolute 23 . From the present data, we conclude that there is a large percentage of children and youth who are anti‐islet autoantibody negative at the time of diabetes onset, suggesting that a significant percentage of children, even those <10 years of age, may have a non‐immune form of diabetes, with a marked increase in non‐immune form of diabetes after 10 years of age.…”

Section: Discussionsupporting

confidence: 60%

“…22 However, some new-onset patients in the present study carried the DQB1*0602 allele and were positive for anti-islet autoantibodies; this has been observed in other studies, suggesting the protective effect associated with DQ*0602 is not absolute. 23 From the present data, we conclude that there is a large percentage of children and youth who are anti-islet autoantibody negative at the time of diabetes onset, suggesting that a significant percentage of children, even those <10 years of age, may have a non-immune form of diabetes, with a marked increase in non-immune form of diabetes after 10 years of age. Autoantibody-negative patients without DR3 ⁄ DR4, >10 years of age and who are obese are likely to have Type 2 diabetes.…”

Section: Discussionsupporting

confidence: 48%

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Analysis of pathogenesis of juvenile new-onset diabetes

Wang

Miao

Wang

et al. 2011

Journal of Diabetes

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Background Measurement of anti-islet autoantibodies at the time of disease onset contributes greatly to the differentiation of Type 1A diabetes with HLA Class II subtyping also contributing. Methods Blood samples were obtained from 900 patients with age from 1 month to 25 years (median age 11.1 years) within 2 weeks of diabetes onset to test anti-islet autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA), insulinoma antigen (IA-2AA), the zinc transporter-8 (ZnT8AA), and islet-cell antibodies (ICA). Polymorphisms of the HLA Class II gene were typed in 547 randomly selected patients. Results Of the 900 subjects analyzed, 145 (16.1%) were negative for all five anti-islet autoantibodies, and autoantibody negativity significantly increased with age: 10.2% (38/372) among children <10 years of age, 14.2% (46/325) in those 10–14 years of age, and 30.1% (61/203) in those >14 years of age (P < 0.001). The prevalence of IA-2AA was the highest among young children. The prevalence of GADA increased with age while the prevalence of IAA was inversely correlated with age. At diagnosis, the subjects with negative antibodies had a higher body mass index (P < 0.001) and less high risk HLA genotype DR3-DQ2/DR4-DQ8 (P < 0.01). Conclusion A large percentage of children and youths negative for all anti-islet autoantibodies at the onset of diabetes are likely to have the non-immune form, especially those without DR3/DR4 and obese patients. Among autoantibody-positive Type 1A patients, IAA and GADA showed a reciprocal prevalence, suggesting differential disease pathogenesis.

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Section: Discussionsupporting

confidence: 60%

Section: Discussionsupporting

confidence: 48%

Analysis of pathogenesis of juvenile new-onset diabetes

Wang

Miao

Wang

et al. 2011

Journal of Diabetes

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“…In 1 T1D patient with HLA-DRB1*1501 [13], it was shown that the HLA-DQB1 allele was *0402 (susceptibility) rather than *0602 (protection), consistent with HLA-DQB1 or a gene centromeric to HLA-DQB1 being the susceptibility locus. However, in 14 T1D patients with HLA-DQB1*0602, the nucleotide sequences were entirely normal [14,15], consistent with the view that the true T1D MHC susceptibility gene is centromeric to HLA-DQB1.…”

Section: Introductionsupporting

confidence: 79%

“…Another alternative explanation is that the patients do not carry HLA-DQB1*0602. However, the second exon of HLA-DQB1 was identical to the reference HLA-DQB1*0602 sequence, as determined by direct sequencing for all the patients studied (n ¼ 6) [15]. Furthermore, all of the subjects were carriers of HLA-DQA1*0102, known to be strongly associated with HLA-DQB1*0602.…”

Section: Discussionmentioning

confidence: 96%

The MHC type 1 diabetes susceptibility gene is centromeric to HLA-DQB1

Husain

Kelly

Eisenbarth

et al. 2008

Journal of Autoimmunity

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“…The above work also led to an interest in HLA DQ function as a means of explaining genetic associations with Type 1 diabetes [51–53]. For example, it is known that the HLA DQ 6.2 molecule protects and HLA DQ 6.4 molecule predisposes to Type 1 diabetes.…”

Section: Development Of Research Interests To Last a Professional Lifmentioning

confidence: 99%

Diabetes—science, serendipity and common sense

Barnett

2011

Diabetic Medicine

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This paper is dedicated to young researchers in diabetes. One such person was Frederick Banting who, with his colleagues, isolated insulin in 1921, saving the lives of literally millions of people. What factors allowed Banting and other scientists to produce work that has immensely benefited the human race? I propose that it is the combination of good scientific background (the 'prepared mind'), commonly some serendipity taken with a good dose of common sense and supplemented by enthusiasm, tenacity and good mentoring, which drives the 'power of observation' and the ability to take forward the good idea. I give examples from history to support this and then discuss some of the 'truths, perspectives and controversies' within the diabetes arena when I first started in diabetes research in the late 1970s. I describe how my appetite was initially 'whetted' for research by moving to an excellent clinical research environment with encouragement to test ideas and controversies initially in a clinical research programme, followed by more scientific ⁄ basic research. The work that I performed as a young doctor and research fellow led to a lifelong professional interest in three major areas-causes and interventions for diabetes vascular disease, studies of the molecular genetics of Type 1 and Type 2 diabetes and work on diabetes in different ethnic groups. I provide a summation of my own and other people's work to demonstrate how research can be progressed and lead to patient benefit as well as providing an incredibly rewarding career. I believe that we need to encourage and put more resources into development of young doctors and scientists wishing to undertake research in our discipline. Areas ripe for much-needed clinical research programmes, for example, include work on best practice ⁄ provision of health care, application of the evidence base from clinical trials to achieve public health gains, attention to adherence issues and better-tolerated therapies. Most importantly, a greater emphasis on prevention through public health measures and 'buy in' from the whole population is urgently required.

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Sequencing of the Second Exon of the MHC Class II DQ6 Alleles in Patients with Type 1 Diabetes

Cited by 7 publications

References 9 publications

Analysis of pathogenesis of juvenile new-onset diabetes

Analysis of pathogenesis of juvenile new-onset diabetes

The MHC type 1 diabetes susceptibility gene is centromeric to HLA-DQB1

Diabetes—science, serendipity and common sense

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