Relationship Between TOMM40 Rs2075650 Polymorphism And Cerebral Infarction

Objective The translocase of outer mitochondrial membrane 40(TOMM40)is a complex formed by the outer membrane transposase,which mediates the transfer of nuclear-encoded proteins from the cytoplasm into the mitochondria.Multiple studies have shown that the single nucleotide polymorphis(SNP)rs2075650 of TOMM40 is closely related to the pathogenesis of Alzheimer’s disease(AD)and coronary artery disease(CAD).Because of the similar pathogenesis among cerebral infarction(CI),AD and CAD,this study was mainly to analyze the the association between the distribution of TOMM40 SNP rs2075650 and the cerebral infarction in Chinese Han population.Methods We performed a case-control study including 507 patients with cerebral infarction and 510 healthy subjects.We selected the case group from patients at the Zhongnan Hospital of Wuhan University.The control group was from the physical examination center of Zhongnan Hospital of Wuhan University.The samples were collected from September 2016 to July 2017.EDTA anticoagulation was collected from all subjects,DNA was manually extracted by SDS lysis,and PCR amplification was performed,and TOMM40 SNP rs2075650 was genotyped by high resolution melting(HRM)technique.Eighty subjects were selected from the case group and the control group.The DNA was extracted by DNA extraction kit,the remaining blood was used to extract RNA by Trizol reagent,and the RNA was reverse-transcribed into CDNA by reverse transcription kit,and then detected by real time quantitative PCR.We calculated the relative expression level of TOMM40 mRNA.Results There were significant differences in the frequency of smoking,alcohol drinking,hypertension,T2 DM,fasting plasma glucose,systolic blood pressure,diastolic blood pressure,total cholesterol,triglyceride,and high-density lipoprotein cholesterol between the case group and the control group(P<0.05).There was no significant difference in age,gender,and low-density lipoprotein cholesterol(P>0.05).There were significant differences in the proportions of allele A and G between the two groups(P<0.05).The proportions of AA,AG and GG were statistically different between the two groups(P<0.05).The effects of SNP rs2075650 on patients with cerebral infarction were further studied.The genotypes of the subjects were divided into dominant models and recessive models.There was a statistically significant difference between the two groups in the proportions of AA and AG+GG genotypes[OR=0.688(95% CI: 0.502,0.942)P=0.019].There was no significant difference between the two groups in the proportions of GG and AG+AA genotypes [OR=2.184(95% CI: 0.824,5.792)P=0.108].After adjusting for confounding factors by multivariate logistic regression analysis,the proportion of AA,AG,GG and the dominant model were no longer statistically different between the two groups(P>0.05).The proportion of A and G between the two groups is still statistically significant(P<0.05).Compared with the control group,the expression level of TOMM40 mRNA in the case group was lower,and there was a statistical difference between the two groups(P<0.05).Compared with individuals carrying the SNP rs2075650 AA genotype,individuals carrying the AG + GG genotype had higher TOMM40 mRNA expression levels,but no statistical differences were found between the two groups(P > 0.05).Conclusions In the Chinese Han population,TOMM40 SNP rs2075650 may interact with smoking,alcohol,hypertension,T2 DM and blood lipids to increase the risk of cerebral infarction.Allele G may have a protective effect on cerebral infarction.