PMID- 11158011
OWN - NLM
STAT- MEDLINE
DCOM- 20010322
LR  - 20111117
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 86
IP  - 2
DP  - 2001 Feb
TI  - Possible human leukocyte antigen-mediated genetic interaction between type 1 and 
      type 2 Diabetes.
PG  - 574-82
AB  - 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.
FAU - Li, H
AU  - Li H
AD  - Diabetes and Endocrine Research Laboratory, Department of Endocrinology, Lund 
      University, S-20502 Malmo, Sweden.
FAU - Lindholm, E
AU  - Lindholm E
FAU - Almgren, P
AU  - Almgren P
FAU - Gustafsson, A
AU  - Gustafsson A
FAU - Forsblom, C
AU  - Forsblom C
FAU - Groop, L
AU  - Groop L
FAU - Tuomi, T
AU  - Tuomi T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Autoantibodies)
RN  - 0 (C-Peptide)
RN  - 0 (HLA-D Antigens)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DQ alpha-Chains)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQA1 antigen)
RN  - 0 (HLA-DQB1 antigen)
RN  - 0 (HLA-DR3 Antigen)
RN  - 0 (HLA-DR4 Antigen)
RN  - 0 (Insulin)
RN  - EC 4.1.1.15 (Glutamate Decarboxylase)
SB  - IM
MH  - Autoantibodies/blood
MH  - C-Peptide/blood
MH  - Diabetes Mellitus, Type 1/blood/*genetics/*immunology
MH  - Diabetes Mellitus, Type 2/blood/*genetics/*immunology
MH  - Female
MH  - Finland
MH  - Genotype
MH  - Glucose Tolerance Test
MH  - Glutamate Decarboxylase/immunology
MH  - HLA-D Antigens/*genetics
MH  - HLA-DQ Antigens/genetics
MH  - HLA-DQ alpha-Chains
MH  - HLA-DQ beta-Chains
MH  - HLA-DR3 Antigen/genetics
MH  - HLA-DR4 Antigen/genetics
MH  - Humans
MH  - Insulin/blood
MH  - Male
MH  - Middle Aged
EDAT- 2001/02/07 11:00
MHDA- 2001/03/27 10:01
CRDT- 2001/02/07 11:00
PHST- 2001/02/07 11:00 [pubmed]
PHST- 2001/03/27 10:01 [medline]
PHST- 2001/02/07 11:00 [entrez]
AID - 10.1210/jcem.86.2.7170 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2001 Feb;86(2):574-82. doi: 10.1210/jcem.86.2.7170.