title: Association of TOMM40 polymorphisms with late-onset Alzheimer's disease in a Northern Han Chinese population.
abstract: Mitochondrial dysfunction is an early defect in the pathogenesis of late-onset Alzheimer's disease (LOAD). One interesting candidate gene for mitochondrial dysfunction in LOAD is the translocase of outer mitochondrial membrane 40 homolog (TOMM40) gene. Several single nucleotide polymorphisms (SNPs) within TOMM40 have been shown to affect susceptibility to LOAD in Caucasians, while there are no studies on the association of the polymorphisms with LOAD risk in Han Chinese. Here, the association of TOMM40 polymorphisms in LOAD was investigated in a large Northern Han Chinese cohort consisting of 1,578 individuals. Both allelic and genotypic associations of three SNPs (rs157580, rs2075650, and rs11556505) with LOAD risk were observed in the total sample as well as in the non- APOE ε4 carriers. For rs1160985, the allele and genotype frequencies differed significantly only in APOE ε4 carriers. After adjustment for age, gender, and APOE ε4 status, the association remained statistically significant only for the rs157580 but not for rs2075650 and rs11556505. In contrast, the rs1160985 exhibited significant risk effect after adjustment. In addition, haplotype analysis confirmed that the haplotypes derived from SNPs in rs2075650, rs11556505, and rs1160985 were associated with either risk or protective effects. In summary, our findings suggest that the TOMM40 polymorphisms may play a role in the pathogenesis of LOAD in Han Chinese.
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No. 5 Donghai Middle Road, Qingdao 266071, China.
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Ma
authors.forename: Jin-Tai
authors.initials: JT
authors.lastname: Yu
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Hui-Fu
authors.initials: HF
authors.lastname: Wang
authors.forename: Qiu-Yan
authors.initials: QY
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Lan
authors.initials: L
authors.lastname: Tan
mesh_terms: D017668:Age of Onset; D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000208:ethnology / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D002681:China / Q000453:epidemiology; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide
chemical_list: D053327:Apolipoprotein E4; D026901:Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; C400783:TOMM40 protein, human