Association Between RAGE Gly82ser Polymorphism, Serum Level Of SRAGE And Mild Cognitive Impairment Of Type 2 Diabetes Mellitus

Background and objectives:As the receptor of advanced glycation end products and amyloid-beta peptides, RAGE is involved in chronic complications of type 2 diabetes mellitus (T2DM) and Alzheimer’s disease. This study aims to investigate the role of soluble RAGE (sRAGE) and the RAGE Gly82Ser polymorphism in Chinese Han T2DM patients with mild cognitive impairment (MCI).Methods:We recruited a total of 167 T2DM patients,82 subjects satisfied the MCI diagnostic criteria and 85 matched individuals with healthy cognition. Multi-dimensional neurological scales were used to extensively assess the cognition of participants. Polymerase chain reaction (PCR) restriction fragment length polymorphism-based genotyping was performed to determine the genotype of RAGE Gly82Ser polymorphism. The serum levels of sRAGE were examined by enzyme-linked immunosorbent assay.Results:(1) Compared with cognitively normal group, type 2 diabetes patients have a higher incidence of arterial plaque group, diabetic nephropathy and coronary heart disease (p<0.05). The case group has a slightly higher levels of uric acid (289.91± 90.63 vs.254.45±71.04, umol/L, p<0.05), sRAGE level of cognitive impairment group was significantly lower than the control group (0.87±0.35 vs.1.05±0.52, ng/ ml, p<0.05); (2) Logistic regression models show uric acid, coronary heart disease, and low level of sRAGE are risk factors of diabetic cognitive impairment, each increased sRAGE of 0.67ng/mL would reduce 42% risk of diabetic cognitive impairment (OR 0.58 [95% CI 0.39-0.86], p=0.007); (3) No significant differences were found between RAGE genotype and allele distributions of the cases and the controls, RAGE levels was significantly lower in case group, especially Gly/Ser subgroup (p<0.05); (4) In MCI subgroup, no differences were found between groups according to different RAGE genotypes(p>0.05).Conclusions:RAGE plays a potential protective role in diabetic cognition impairment. Further studies with larger sample size or longitudinal studies are needed to verify these initial observations and the role of RAGE Gly82Ser in cognitive impairment of type 2 diabetes mellitus.