The Association Between The Common Variations Of ApoE And TRIP4 Genes And Alzheimer Disease

Background: Alzheimer disease(AD) is a neurodegenerative illness that currently affects 6.0 million Chineses with numbers projected to grow to over 20 million by mid-century and 5.3 million Americans projected to grow to over 10 million by mid-century. The genetics of AD is subdivided into early-onset AD(EOAD) and late-onset AD(LOAD).EOAD usually follows an autosomal dominant inheritance pattern where mutations in a single gene can cause the disease. Mutations in presenilin 1(PSEN1), presenilin 2(PSEN2),and amyloid precursor protein(APP)have been reported in development of EOAD. The genetics of LOAD is more complex involving multiple genes with only modest familial aggregation. Apolipoprotein E(Apo E) is the most well-established gene associated with LOAD where individuals with e4 allele(Apo E ε4) have a substantially higher risk of developing AD. Genome-wide associations studies(GWAS) have identified over 20 additional genetic loci for LOAD.The relationship between alterations in thyroid function and cognitive deficits has been investigated in several previous studies. Hypo-or hyperthyroidism and, to a lesser extent, subclinical thyroid dysfunction can negatively affect cognitive performance. Metaanalysis data of IGAP meta-analysis have identified TRIP4 as a novel genome-wide significant locus. However, limited data are available on the potential association of thyroid function with mild MCI and AD in the elderly Chinese population. At present, researches about the TRIP4 gene have not been found in Chinese population.Objective To explore association between the common variations of Apo E and TRIP4(rs4776494) genes and Alzheimer disease risk in Chinese people. Method A case-control method was performed, consisting of 77 patients with Alzheimer disease and 80 controls which are matched at age and gender with the patients. PCR and sequencing were used to determine the distribution of allele and genotype frequency of TRIP4(rs4776494). Every case was tested with the Mini-Mental State Examinations(MMSE),Clinical Dementia Rating(CDR) and behavioral and psychological symptoms of dementia(BPSD). Result The distribution of Apo Eε4 genotype is significantly different between cases and controls(P<0.01); Cases with Apo Eε4 allele performed high score in MMSE than those without Apo Eε4 allele(p<0.01); Frequency of Allele T of TRIP4(rs4776494) was higher in cases than controls(P<0.01); Cases with TRIP4 T allele showed higher rate of BPSD than those without TRIP4 allele(P<0.05). Conclusion Apo Eε4 and allele T of TRIP4(rs4776494) might be genetics risk factors of Alzheimer disease risk in Chinese population. Apo Eε4 gene polymorphism is associated with cognitive function; To some degree, TRIP4 genes may promote the occurrence of mental symptoms in AD cases.