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

Authors :
Williams RC
Muller YL
Hanson RL
Knowler WC
Mason CC
Bian L
Ossowski V
Wiedrich K
Chen YF
Marcovina S
Hahnke J
Nelson RG
Baier LJ
Bogardus C
Source :
Diabetologia [Diabetologia] 2011 Jul; Vol. 54 (7), pp. 1684-92. Date of Electronic Publication: 2011 Apr 12.
Publication Year :
2011

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.<br />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.<br />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.<br />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.

Details

Language :
English
ISSN :
1432-0428
Volume :
54
Issue :
7
Database :
MEDLINE
Journal :
Diabetologia
Publication Type :
Academic Journal
Accession number :
21484216
Full Text :
https://doi.org/10.1007/s00125-011-2122-8