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. 2011 Jul;54(7):1684-92.
doi: 10.1007/s00125-011-2122-8. Epub 2011 Apr 12.

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

R C Williams  1 , 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
Affiliations

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

R C Williams et al. Diabetologia. 2011 Jul.

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.

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Conflict of interest statement

Duality of interest The authors declare that there is no duality of interest associated with this manuscript.

Figures

Fig. 1
Fig. 1
Mean concentrations of insulin (a) and glucose (b) in 266 participants with normal glucose tolerance stratified by the presence (squares) or absence (triangles) of HLA-DRB1*02(1602) (n=33) during an IVGTT. Insulin secretion was higher for persons with DRB1*02 during the test. After adjusting for age, sex, body fat percentage and insulin sensitivity, AIR was higher in persons with DRB1*02 (p=0.005, Table 4)
Fig. 2
Fig. 2
Plasma concentrations of insulin (a) and glucose (b) after a 75 g OGTT in 266 participants with normal glucose tolerance stratified by the presence (squares) or absence (triangles) of HLA-DRB1* 02(1602). After adjusting for covariates age, sex, body fat percentage, 30 min glucose and insulin sensitivity, the 30 min insulin concentration was higher (p=0.017, Table 4) for those with DRB1*02
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