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Possible human leukocyte antigen-mediated genetic interaction between type 1 and type 2 Diabetes

Li, Haiyan LU ; Lindholm, Eero LU ; Almgren, Peter LU ; Gustafsson, A; Forsblom, C; Groop, Leif LU and Tuomi, T (2001) In Journal of Clinical Endocrinology and Metabolism 86(2). p.574-582
Abstract
We assessed the prevalence of families with both type 1 and type 2 diabetes in Finland; and we studied, in patients with type 2 diabetes, the association between a family history of type 1 diabetes, glutamic acid decarboxylase (GAD) antibodies (GADab), and type 1 diabetes-associated human leukocyte antigen (HLA) DQB1-genotypes. Further, in mixed type 1/type 2 diabetes families, we investigated whether sharing an HLA haplotype with a family member with type 1 diabetes influenced the manifestation of type 2 diabetes. Among 695 families ascertained through the presence of more than 1 patient with type 2 diabetes, 100 (14%) also had members with type 1 diabetes. Type 2 diabetic patients from the mixed families had, more often, GADab (18% vs.... (More)
We assessed the prevalence of families with both type 1 and type 2 diabetes in Finland; and we studied, in patients with type 2 diabetes, the association between a family history of type 1 diabetes, glutamic acid decarboxylase (GAD) antibodies (GADab), and type 1 diabetes-associated human leukocyte antigen (HLA) DQB1-genotypes. Further, in mixed type 1/type 2 diabetes families, we investigated whether sharing an HLA haplotype with a family member with type 1 diabetes influenced the manifestation of type 2 diabetes. Among 695 families ascertained through the presence of more than 1 patient with type 2 diabetes, 100 (14%) also had members with type 1 diabetes. Type 2 diabetic patients from the mixed families had, more often, GADab (18% vs. 8%, P < 0.0001) and DQB1*0302/X genotype (25% vs. 12%, P = 0.005) than patients from families with only type 2 diabetes; but they had a lower frequency of DQB1*02/0302 genotype, compared with adult-onset type 1 patients (4% vs. 27%, P < 0.0001). In the mixed families, the insulin response to oral glucose load was impaired in patients who had HLA class II risk haplotypes, either DR3(17)-DQA1*0501-DQB1*02 or DR4*0401/4-DQA1*0301-DQB1*0302, compared with patients without such haplotypes (P = 0.016). This finding was independent of the presence of GADab. We conclude that type 1 and type 2 diabetes cluster in the same families. A shared genetic background with a patient with type 1 diabetes predisposes type 2 diabetic patients both to autoantibody positivity and, irrespective of antibody positivity, to impaired insulin secretion. The findings support a possible genetic interaction between type 1 and type 2 diabetes mediated by the HLA locus. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Clinical Endocrinology and Metabolism
volume
86
issue
2
pages
574 - 582
publisher
The Endocrine Society
external identifiers
  • pmid:11158011
  • scopus:0035092748
ISSN
1945-7197
language
English
LU publication?
yes
id
c6a96b87-a3ba-4a3f-ac89-9cfdc0d0ab45 (old id 1121793)
alternative location
http://jcem.endojournals.org/cgi/content/abstract/86/2/574
date added to LUP
2008-04-30 12:23:40
date last changed
2018-05-29 11:42:36
@article{c6a96b87-a3ba-4a3f-ac89-9cfdc0d0ab45,
  abstract     = {We assessed the prevalence of families with both type 1 and type 2 diabetes in Finland; and we studied, in patients with type 2 diabetes, the association between a family history of type 1 diabetes, glutamic acid decarboxylase (GAD) antibodies (GADab), and type 1 diabetes-associated human leukocyte antigen (HLA) DQB1-genotypes. Further, in mixed type 1/type 2 diabetes families, we investigated whether sharing an HLA haplotype with a family member with type 1 diabetes influenced the manifestation of type 2 diabetes. Among 695 families ascertained through the presence of more than 1 patient with type 2 diabetes, 100 (14%) also had members with type 1 diabetes. Type 2 diabetic patients from the mixed families had, more often, GADab (18% vs. 8%, P &lt; 0.0001) and DQB1*0302/X genotype (25% vs. 12%, P = 0.005) than patients from families with only type 2 diabetes; but they had a lower frequency of DQB1*02/0302 genotype, compared with adult-onset type 1 patients (4% vs. 27%, P &lt; 0.0001). In the mixed families, the insulin response to oral glucose load was impaired in patients who had HLA class II risk haplotypes, either DR3(17)-DQA1*0501-DQB1*02 or DR4*0401/4-DQA1*0301-DQB1*0302, compared with patients without such haplotypes (P = 0.016). This finding was independent of the presence of GADab. We conclude that type 1 and type 2 diabetes cluster in the same families. A shared genetic background with a patient with type 1 diabetes predisposes type 2 diabetic patients both to autoantibody positivity and, irrespective of antibody positivity, to impaired insulin secretion. The findings support a possible genetic interaction between type 1 and type 2 diabetes mediated by the HLA locus.},
  author       = {Li, Haiyan and Lindholm, Eero and Almgren, Peter and Gustafsson, A and Forsblom, C and Groop, Leif and Tuomi, T},
  issn         = {1945-7197},
  language     = {eng},
  number       = {2},
  pages        = {574--582},
  publisher    = {The Endocrine Society},
  series       = {Journal of Clinical Endocrinology and Metabolism},
  title        = {Possible human leukocyte antigen-mediated genetic interaction between type 1 and type 2 Diabetes},
  volume       = {86},
  year         = {2001},
}