Correlation Between Obesity And Cognitive Function Related Genes And Their Interaction With Mild Cognitive Impairment

Objective Mild cognitive impairment(MCI)is a clinical pathological condition between normal cognitive aging and dementia,and the predictors of MCI has been identified by previous studies include obesity,hypertension and genetic variants.However,the interaction of environmental factors and genes on the risk of MCI under reported.This study aims to explore the association between obesity,gene polymorphisms,as well as their interactions with MCI,and to provide evidence for precision prevention of cognitive impairment.Methods This study is designed as prevalence-based case-control analysis.Residents aged 55 and over who participated in the regular community public health examination in Ningxia from 2013 to 2016 were included.Trained medical students were hired to administrate cognitive assessment using the Mini-Mental State Examination(MMSE)in the primary health care centers.Physical examination was given by the community health care providers,including height and weight.Fasting venous blood sample collected for blood glucose testing,and the DNA samples were extracted for gene polymorphisms test.MassARRAY time-of-flight mass spectrometry system was used to detect the gene polymorphisms,and all tests were performed by Xi’an Huada Gene Testing Company according to standard procedures.Obesity is defined according to the"Guidelines for the Prevention and Control of Overweight and Obesity in Chinese Adults",and a body mass index(BMI)of 28 kg/m~2 or more is determined to be obesity.The MCI is determined according to Peterson’s criteria and taking into account the education attainment as:illiterate,MMSE≤17 points,primary school MMSE≤20 points,middle school and above MMSE≤24 points.Unconditional logistic regression model and multifactor dimensionality reduction(MDR)were employed to exam the interactions between obesity and genes,genes and genes.Results1.A total of 2,845 subjects completed the physical examination and cognitive function assessment,and 2,555 subjects completed the genetic polymorphism test and were included in the final analysis.The average age was(64.36±5.52)years.Among them,444(17.4%)subjects met the MCI criteria.400subjects met the criteria for obesity,with a prevalence of 15.7%.The univariate analysis showed that,compared with the non-MCI group,the average age of the MCI group was older(66.03±6.33 vs 64.00±5.25),t=7.13,P<0.001;the GDS score was higher(6.64±6.16 vs 5.29±5.56),t=4.37,P<0.001;ADL score was higher(17.04±5.68 vs 14.87±2.66),t=9.81,P<0.001;educational attainment,marriages times,and non-alcoholic fatty liver composition ratio were statistically different(P<0.05);there was no statistically significant difference in the proportion of living alone,hypertension,and fasting blood glucose in the two groups(P>0.05).2.After controlling general demographic data(age,gender,education,marital status,living alone)and physical health factors(hypertension,abnormal fasting blood glucose,non-alcoholic fatty liver),the results of non-conditional logistic regression analysis suggest:obesity(OR=1.42,CI95%:1.04-1.94),rs2075650G allele carrying(OR=17.95,CI95%:1.32-244.95),rs11556505T allele carrying(OR=0.06,CI95%:0.01-0.87)were significantly related with MCI.3.MDR results showed a strong antagonistic effect between obesity and rs4402960(OR=1.62,CI95%:1.37-1.92),and a weak synergy between obesity and rs7901695(OR=1.67,CI95%:1.41-1.97).Hierarchical analysis showed there was no association between obesity and MCI in the rs4402960T allele carrier group(P>0.05),obesity is a risk factor for MCI in non-rs4402960T allele carrier group(OR=1.55,CI95%:1.02-2.35).Conclusions1.The prevalence of MCI is higher in people aged 55 and older in the community.The obesity,age,gender,and polymorphisms of multiple genes were significantly associated with the risk of MCI.In terms to the genetic variants,the rs11556505T allele of the TOMM40 gene carries is independent protective factors,while the rs2075650G allele carries is independent risk factors for MCI.2.The interaction between obesity and genes may play a role in the occurrence of MCI.The strong antagonism between obesity and insulin-like growth factor 2 mRNA binding protein 2 recombinant protein(IGF2BP2)gene(rs4402960)will reduce the pathogenic effect of obesity in MCI.