Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 1550 East Indian School Road, Phoenix, AZ 85014, USA.
Diabetologia. 2011 Jul;54(7):1684-92. doi: 10.1007/s00125-011-2122-8. Epub 2011 Apr 12.
AIMS/HYPOTHESIS: We sought to identify the physiological implications of genetic variation at the HLA-DRB1 region in full-heritage Pima Indians in Arizona.
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.
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.
目的/假设：我们试图确定在亚利桑那州的全血统皮马印第安人中 HLA-DRB1 区域的遗传变异对骨骼肌 mRNA 表达 HLA-DRB1 和 HLA-DRA 以及 2 型糖尿病和糖尿病前期特征的生理影响。
检测 6p 染色体 HLA 区域的单核苷酸多态性与骨骼肌 HLA-DRB1 和 HLA-DRA 的 mRNA 表达以及 2 型糖尿病和糖尿病前期特征之间的关联。
rs9268852 处的 A 等位基因，标记 HLA-DRB1 02(1602)，与 HLA-DRB1 mRNA 表达升高（n=133，p=4.27×10(-14))和 2 型糖尿病风险降低相关（n=3265，OR 0.723，p=0.002）。在葡萄糖耐量正常的人群中（n=266），该等位基因与静脉葡萄糖耐量试验期间更高的平均急性胰岛素反应相关（p=0.005）、口服葡萄糖耐量试验期间更高的平均 30 分钟胰岛素浓度相关（p=0.017）和更高的体脂百分比相关（p=0.010）。该多态性与 HLA-DRA mRNA 表达或胰岛素敏感性无关。
结论/解释：HLA-DRB1*02 对 2 型糖尿病具有保护作用，可能通过增强自身耐受性，从而防止自身免疫介导的胰岛素分泌减少。
