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Genetic and immunological findings in patients with newly diagnosed insulin-dependent diabetes mellitus

Kockum, Ingrid ; Lernmark, Å LU ; Dahlquist, Gisela ; Falorni, A. ; Hagopian, W. A. ; Landin-Olsson, Mona LU ; Li, L. C. ; Luthman, H. LU ; Palmer, J. P. LU and Sanjeevi, C. B. , et al. (1996) In Hormone and Metabolic Research 28(7). p.344-347
Abstract

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... (More)

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 affects the risk for IDDM associated with HLA, other IDDM genes as well as commonly used immunological markers for IDDM.

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type
Contribution to journal
publication status
published
subject
keywords
anti-GAD, HLA, ICA, IDDM
in
Hormone and Metabolic Research
volume
28
issue
7
pages
344 - 347
publisher
Georg Thieme Verlag KG
external identifiers
  • pmid:8858382
  • scopus:8944236085
ISSN
0018-5043
DOI
10.1055/s-2007-979811
language
English
LU publication?
yes
id
3f771499-6954-4521-a5aa-1d9a46964a21
date added to LUP
2019-07-01 13:20:46
date last changed
2021-02-17 01:11:52
@article{3f771499-6954-4521-a5aa-1d9a46964a21,
  abstract     = {<p>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 (&gt; 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 affects the risk for IDDM associated with HLA, other IDDM genes as well as commonly used immunological markers for IDDM.</p>},
  author       = {Kockum, Ingrid and Lernmark, Å and Dahlquist, Gisela and Falorni, A. and Hagopian, W. A. and Landin-Olsson, Mona and Li, L. C. and Luthman, H. and Palmer, J. P. and Sanjeevi, C. B. and Sundkvist, G. and Östman, J.},
  issn         = {0018-5043},
  language     = {eng},
  month        = {01},
  number       = {7},
  pages        = {344--347},
  publisher    = {Georg Thieme Verlag KG},
  series       = {Hormone and Metabolic Research},
  title        = {Genetic and immunological findings in patients with newly diagnosed insulin-dependent diabetes mellitus},
  url          = {http://dx.doi.org/10.1055/s-2007-979811},
  doi          = {10.1055/s-2007-979811},
  volume       = {28},
  year         = {1996},
}