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HLA-DRB1 reduces the risk of type 2 diabetes mellitus by increased insulin secretion.
- 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.
- Subjects :
- Diabetes Mellitus, Type 2 metabolism
Female
Genetic Predisposition to Disease
HLA-DR Antigens metabolism
HLA-DR alpha-Chains
HLA-DRB1 Chains
Humans
Insulin Secretion
Male
Muscle, Skeletal metabolism
Polymorphism, Single Nucleotide genetics
Diabetes Mellitus, Type 2 genetics
HLA-DR Antigens genetics
Insulin metabolism
Subjects
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