Associations between apolipoprotein E gene polymorphisms and Alzheimer’s disease risk in a large Chinese Han population

Abstract

ObjectiveApolipoprotein E gene (APOE) polymorphisms contributing to the risk of sporadic Alzheimer’s disease (AD) have been identified for decades, but it has not been investigated in large AD samples of Chinese Han population.MethodsWe performed a cross-sectional study to explore the effect of APOE polymorphisms on sporadic AD in 875 sporadic AD patients and 1,195 cognitive normal controls of Chinese Han. Genotyping of APOE was determined by multiplex amplification refractory mutation system polymerase chain reaction.ResultsAPOE ε3ε4 and ε4ε4 genotypes increased AD risk with dosage effect. The odds ratio (OR) of ε3ε4 was 1.89 and the OR of ε4ε4 was 15.64 compared with that of ε3ε3 in all the subjects. E2ε3 genotype decreased AD risk in all the subjects (OR=0.64), female subgroup (OR=0.57), and late-onset AD subgroup (OR=0.60). However, neither ε2ε2 nor ε2ε4 affected AD risk. About the age at onset (AAO), the influence of APOE ε4 was only exhibited in late-onset AD subgroup, with 1 year lower in ε4-positive ones than negative ones. Further analysis did not show the dosage effect of ε4 pertinent to AAO, though the AAO of ε4ε4 patients decreased by 2 years. E2 did not affect the AAO of AD.ConclusionAPOE ε4 is a strong risk factor of AD risk in Chinese Han population, and APOE ε4ε4 genotype might be related to the AAO of late-onset AD.

Identifying novel genetic variants for brain amyloid deposition: a genome-wide association study in the Korean population

“…We observed a stronger effect of the variant in APOE (rs429358) on Aβ positivity in the Korean population than that in the European population (Korean, OR = 5.275; European, OR = 1.197 [11]). This is similar to the results in previous studies of the East Asian population, in which the effect of APOE ɛ4 on AD risk was stronger in Han Chinese [48] and Japanese [47] than in the European population. Furthermore, outside the APOE locus, previously reported Aβ associated SNPs in European ancestry data were not replicated [11] in our cohort.…”

APOE Promoter Polymorphism-219T/G is an Effect Modifier of the Influence of APOE ε4 on Alzheimer’s Disease Risk in a Multiracial Sample

“…Although the APOE ε4 allele is one of the most well-established AD risk factors and the genetic variant that by far confers the strongest effect on disease risk [6,10,49], most studies of this association in non-EuroA populations have not precisely quantified for APOE genotype-associated risks for ε4 heterozygotes and ε4 homozygotes with notable exceptions of AAs [10,27], Caribbean Hispanics [50], Indians [51], and Han Chinese [52]. Similar to Chinese [52], our study showed that the effect of ε4 on AD risk was stronger in Koreans and Japanese than in EuroAs and other non-EuroA populations, including AAs, Indians, and Israeli-Arabs [53]. Ethnic differences in the effect size of this association might be due to differences in allele frequency such that the proportional difference in the ε4 frequency between cases and controls resulted in a larger odds ratio even though the absolute difference in the allele frequency was similar across the population.…”

Associations between APOE polymorphisms and seven diseases with cognitive impairment including Alzheimer’s disease, frontotemporal dementia, and dementia with Lewy bodies in southeast China

“…Its encoding protein, Apolipoprotein E, consists of 299 amino acids and is a cholesterol carrier involving in lipid transportation and injury repair in the brain. APOE ε4 increased the risk of AD in a dose-dependent manner, in contrast to APOE ε 2, which plays a protective role ( Bertram et al , 2007 ; Sando et al , 2008 ; Bonner-Jackson et al , 2012 ; Wu et al , 2015 ).…”