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Genetic Discrimination Between LADA and Childhood-Onset Type 1 Diabetes Within the MHC

Mishra, Rajashree (author)
University of Pennsylvania,The Children's Hospital of Philadelphia
Åkerlund, Mikael (author)
Lund University,Lunds universitet,Diabetiska komplikationer,Forskargrupper vid Lunds universitet,Diabetic Complications,Lund University Research Groups,Skåne University Hospital
Cousminer, Diana L. (author)
The Children's Hospital of Philadelphia,University of Pennsylvania
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Ahlqvist, Emma (author)
Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,Skåne University Hospital
Bradfield, Jonathan P. (author)
The Children's Hospital of Philadelphia
Chesi, Alessandra (author)
The Children's Hospital of Philadelphia
Hodge, Kenyaita M. (author)
The Children's Hospital of Philadelphia
Guy, Vanessa C. (author)
The Children's Hospital of Philadelphia
Brillon, David J. (author)
Cornell University
Pratley, Richard E. (author)
Florida Hospital
Rickels, Michael R. (author)
University of Pennsylvania
Vella, Adrian (author)
Mayo Clinic Minnesota
Ovalle, Fernando (author)
University of Alabama
Harris, Ronald I. (author)
Geisinger Health System
Melander, Olle (author)
Lund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups,Skåne University Hospital
Varvel, Stephen (author)
Health Diagnostic Laboratory, Inc.
Hakonarson, Hakon (author)
University of Pennsylvania,The Children's Hospital of Philadelphia
Froguel, Phillippe (author)
University of Lille,Imperial College London
Lonsdale, John T. (author)
National Disease Research Interchange
Mauricio, Didac (author)
CIBER Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM),Hospital de Sant Pau
Schloot, Nanette C. (author)
German Diabetes Research Institute
Khunti, Kamlesh (author)
University of Leicester
Greenbaum, Carla J. (author)
Benaroya Research Institute
Yderstræde, Knud B. (author)
Odense University Hospital
Tuomi, Tiinamaija (author)
Folkhälsan Research Center,Helsinki University Central Hospital,University of Helsinki
Voight, Benjamin F. (author)
University of Pennsylvania
Schwartz, Stanley (author)
Main Line Health
Boehm, Bernhard O. (author)
University Hospital of Ulm,Imperial College London,Nanyang Technological University
Groop, Leif (author)
Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,Skåne University Hospital,Institute for Molecular Medicine Finland (FIMM)
Leslie, Richard David (author)
Barts Health NHS Trust,Queen Mary University
Grant, Struan F.A. (author)
The Children's Hospital of Philadelphia,University of Pennsylvania
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 (creator_code:org_t)
2019-12-16
2020
English 8 s.
In: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 43:2, s. 418-425
Related links:
http://dx.doi.org/10...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • OBJECTIVE: The MHC region harbors the strongest loci for latent autoimmune diabetes in adults (LADA); however, the strength of association is likely attenuated compared with that for childhood-onset type 1 diabetes. In this study, we recapitulate independent effects in the MHC class I region in a population with type 1 diabetes and then determine whether such conditioning in LADA yields potential genetic discriminators between the two subtypes within this region. RESEARCH DESIGN AND METHODS: Chromosome 6 was imputed using SNP2HLA, with conditional analysis performed in type 1 diabetes case subjects (n = 1,985) and control subjects (n = 2,219). The same approach was applied to a LADA cohort (n = 1,428) using population-based control subjects (n = 2,850) and in a separate replication cohort (656 type 1 diabetes case, 823 LADA case, and 3,218 control subjects). RESULTS: The strongest associations in the MHC class II region (rs3957146, β [SE] = 1.44 [0.05]), as well as the independent effect of MHC class I genes, on type 1 diabetes risk, particularly HLA-B*39 (β [SE] = 1.36 [0.17]), were confirmed. The conditional analysis in LADA versus control subjects showed significant association in the MHC class II region (rs3957146, β [SE] = 1.14 [0.06]); however, we did not observe significant independent effects of MHC class I alleles in LADA. CONCLUSIONS: In LADA, the independent effects of MHC class I observed in type 1 diabetes were not observed after conditioning on the leading MHC class II associations, suggesting that the MHC class I association may be a genetic discriminator between LADA and childhood-onset type 1 diabetes.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

Keyword

ANDIS
diabetes
Diabetics

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