SLC26A4, TFAM Gene Polymorphism And Late-onset Alzheimer’s Disease In A Han Chinese Population

Alzheimer’s disease (AD) is a common age-associated progressiveneurodegenerative disorder. Although the etiology of AD remains poorlyunderstood, genetic factors explain about60-80%of the heritability ofAD. Several gene mutations, namely in β-amyloid precursor protein,presenilin1, and presenilin2, have been associated with the early-onsetfamilial form of Alzheimer’s disease. In contrast to early-onset AD, thegenetic component of susceptibility to late-onset Alzheimer’s disease(LOAD) seems to be more complex. Multiple genetic factors are believedto be involved in the pathogenesis and development of the disorder. Onlythe ε4allele of apolipoprotein E (APOE) gene is definitively associatedwith increased susceptibility to LOAD. However, about half the peoplecarrying at least one ε4allele do not develop LOAD and42%of patientswith LOAD do not possess an APOE ε4allele. Much effort has been madeto search for additional genes that confer LOAD-susceptibility.1. association betweenSLC26A4gene polymorphism and late-onsetAlzheimer’s disease：In a recent genome-wide association study, theSLC26A4gene rs2072064polymorphism was found to be associated withlate-onset Alzheimer’s disease (LOAD) in Caucasians. Here, weinvestigated this association in a large Northern Han Chinese cohortconsisting of599sporadic LOAD patients and598healthy controls matchedfor sex and age in a Northern Han Chinese population from Qingdao, China.Genotyping by the polymerase chain reaction-ligase detection reactionrevealed that there were significant differences in the genotype (P=0.017) and allele (P=0.007) frequencies of the rs2072064polymorphismbetween LOAD patients and controls. The A allele of this polymorphism was significantly associated with a reduced risk of LOAD (odds ratio (OR)=0.792,95%confidence interval (CI)=0.670–0.937, P=0.007). When thedata were stratified by the apolipoprotein E (APOE) ε4status, there wasa significant difference only among APOE ε4non-carriers (genotypic P=0.001, allelic P=0.001). Furthermore, the association betweenrs2072064and LOAD remained significant by logistic regression analysisafter adjustment for age, gender, and the APOE ε4carrier status(dominant model: OR=0.787,95%CI=0.619–1.000, P=0.050; recessivemodel: OR=0.655,95%CI=0.448–0.959, P=0.030; additive model: OR=0.792,95%CI=0.661–0.950, P=0.012). These findings suggest thatSLC26A4is a susceptibility gene for LOAD in a Northern Han Chinesepopulation from the Qingdao area.2. association betweenSLC26A4gene polymorphism and late-onsetAlzheimer’s disease：been proved to contribute to the development ofAlzheimer’s disease (AD).Mitochondrial transcription factor A (TFAM)plays an important role in the maintenance of mtDNA integrity. Recently,some studies suggested two single nucleotide polymorphisms (SNPs)(rs1937and rs2306604) in the TFAM gene are associated with sporadic late-onsetAD (LOAD) in Caucasians. To explore the correlation between TFAM gene andLOAD, we performed a case-control study in a large Chinese cohortconsisting of394patients and390healthy controls. The results showedthat there were significant differences in genotype (P=0.03) and allele(P=0.04) frequencies of the SNP rs1937between LOAD patients and controls.The minor C allele of rs1937acted as a moderate protective factor of LOAD(P=0.04, odds ratios/OR=0.76). The logistic regression analysis alsosuggested an association of LOAD with SNP rs1937(dominant model: P=0.03,OR=0.71; recessive model: P=0.02, OR=0.25; additive model: P=0.01,OR=0.68). No significant association was observed between rs2306604andLOAD. Haplotype analysis identified the haplotype CC as a protective factor of LOAD (P=0.038, OR=0.76). This study provides the evidence thatvariations in TFAM are involved in the pathogenesis of sporadic LOAD inthe Han Chinese populationThis research work enriched the data between Alzheimer’s disease andcandidate gene in China, and we discovered the association between SLC26A4gene rs2072064TFAM gene rs1937site polymorphism and late onsetAlzheimer’s disease in the northern han people. Our study makes peopleto explore AD etiology and pathogenesis further more from genepolymorphism level, and provides important data for future geneticdiagnosis and treatment to.