Correlation Between Endocytosis Genes And Sporadic Alzheimer's Disease In Mongolian And Han Nationalities In Inner Mongolia

Objective To explore the susceptibility of endocytosis related gene polymorphism in Mongolian and Han sporadic Alzheimer's disease(SAD)population in Inner Mongolia Autonomous Region,in order to provide scientific basis for the early diagnosis and treatment of SAD.Methods Case control study was used to collect SAD samples of 506 cases and239 cases of Mongolian and Han nationality aged 55 and over in Inner Mongolia Autonomous Region,and 385 cases of Mongolian and 190 cases of Han nationality matched with age and gender in the same region.Through literature search and bioinformatics analysis,candidate SNPs of endocytosis genes(PICALM,BIN1,CD2AP)were screened out,which were not reported in association with ad in Chinese minorities.The PCR-HRM(Polymerase Chain Reaction-High Resolution Rate Dissolution Curve)was used to detect the genotyping of the study population,and the accuracy of the typing results was verified by random sampling sequencing.SPSS21.0and Haploview were used to analyze the distribution of allele,genotype and genetic model frequency in the two groups,and to verify the association between candidate loci and SAD risk of Mongolian and Han nationalities in Inner Mongolia Autonomous Region.Results(1)There was a significant difference in age between the Mongolian SAD group and the control group(P <0.005),but there was no such difference in the Han population(P>0.05);There were significant differences in different subtypes of APOE between the Mongolian and Han SAD groups and the control group(P <0.005);The APOE genotypes and allele frequencies were significantly different between the Mongolian and Han SAD groups and the control group(P <0.005),and the number of ApoE?4 allele carriers in the Mongolian and Han SAD groups and the control group were significantly different(P<0.005).(2)Among the Mongolian people,The distribution of PICALM rs592297,rs17817600 and rs677909 genotypes between SADgroup and control group was statistically significant(P<0.05);The distribution of genotype frequency of CD2 AP rs9349407 and rs10948363 between SAD group and control group was statistically significant(P < 0.05).After adjusting the carrying status of ApoE ? 4,the difference still existed in ApoE ? 4(-)group(P < 0.05);There was no significant difference between SAD group and control group in genotype and allele frequency of BIN1 rs7561528,rs6733839,rs744373(P > 0.05).(3)Among the Han people,the distribution of genotype frequencies and allele frequencies of BIN1rs7561528,rs744373,rs6733839 and PICALM rs17817600 in SAD group and control group showed no significant difference(P> 0.05).There were differences in PICALM rs592297 and rs677909 genotypes and allele frequencies between the two groups(P<0.05),and the difference was still present in the ApoE ?4(-)group after adjustment for the ApoE ?4 carrier status(P <0.05).There was no significant difference between the two groups in genotype and allele frequencies of CD2 AP rs10948363 and rs9349407(P > 0.05),but after the APOE ? 4 carrier status was corrected,there was significant difference in genotype frequencies of rs10948363 and rs9349407(P < 0.05)in ApoE ? 4(-).(4)Haplotype analysis revealed that “TTTC”,”TCCT”haplotypes were significantly associated with Han SAD(P< 0.05).Conclusion(1)The polymorphism of ApoE gene is related to the susceptibility of sad in Mongolian and Han nationalities in Inner Mongolia Autonomous Region.ApoE 4 can increase the risk of sad in Mongolian and Han nationalities in Inner Mongolia Autonomous Region.(2)PICALM gene polymorphism is related to the susceptibility of SAD in Han and Mongolian populations in Inner Mongolia Autonomous Region:rs17817600 is not related to the incidence of SAD in the Han population in the area;rs17817600,rs692297,and rs677909 are related to the incidence of SAD in the Mongolian population;rs677909 and rs592297 are related to the incidence of SAD in the Han nationality in the area.There are linkage disequilibrium between some SNP loci of PICALM gene.Among them,haplotypes TTTC and TCCT composed of rs149406961,rs592297,rs677909,rs3851179 are related to the risk of SAD in Hannationality.(3)CD2AP gene polymorphisms(rs9349407,rs10948363)are associated with the risk of SAD in Mongolians in the Inner Mongolia Autonomous Region;in the ApoE ?4(-)group,the CD2 AP gene is associated with the incidence of SAD in Mongolians and Hans.(4)BIN1 gene polymorphisms(rs7561528,rs6733839,rs744373)were not related to the risk of SAD in Mongolian and Han ethnic groups in the Inner Mongolia Autonomous Region.