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Diabetologia
Published in: Diabetologia 7/2011

01-07-2011 | Article

HLA-DRB1 reduces the risk of type 2 diabetes mellitus by increased insulin secretion

Authors: R. C. Williams, Y. L. Muller, R. L. Hanson, W. C. Knowler, C. C. Mason, L. Bian, V. Ossowski, K. Wiedrich, Y. F. Chen, S. Marcovina, J. Hahnke, R. G. Nelson, L. J. Baier, C. Bogardus

Published in: Diabetologia | Issue 7/2011

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Abstract

Aims/hypothesis

We sought to identify the physiological implications of genetic variation at the HLA-DRB1 region in full-heritage Pima Indians in Arizona.

Methods

Single-nucleotide polymorphisms from the HLA region on chromosome 6p were tested for association with skeletal muscle mRNA expression of HLA-DRB1 and HLA-DRA, and with type 2 diabetes mellitus and prediabetic traits.

Results

The A allele at rs9268852, which tags HLA-DRB1*02(1602), was associated both with higher HLA-DRB1 mRNA expression (n = 133, p = 4.27 × 10−14) and decreased risk of type 2 diabetes (n = 3,265, OR 0.723, p = 0.002). Among persons with normal glucose tolerance (n = 266) this allele was associated with a higher mean acute insulin response during an intravenous glucose tolerance test (p = 0.005), higher mean 30 min insulin concentration during an oral glucose tolerance test (p = 0.017) and higher body fat percentage (p = 0.010). The polymorphism was not associated with HLA-DRA mRNA expression or insulin sensitivity.

Conclusions/interpretation

HLA-DRB1*02 is protective for type 2 diabetes, probably by enhancing self tolerance, thereby protecting against the autoimmune-mediated reduction of insulin secretion.
Appendix
Available only for authorised users
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Metadata
Title
HLA-DRB1 reduces the risk of type 2 diabetes mellitus by increased insulin secretion
Authors
R. C. Williams
Y. L. Muller
R. L. Hanson
W. C. Knowler
C. C. Mason
L. Bian
V. Ossowski
K. Wiedrich
Y. F. Chen
S. Marcovina
J. Hahnke
R. G. Nelson
L. J. Baier
C. Bogardus
Publication date
01-07-2011
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 7/2011
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-011-2122-8

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