Association between apolipoprotein E gene polymorphism and mild cognitive impairment: a meta-analysis

Yunxia Jiang; Tao He; Wenshuai Deng; Peng Sun

doi:10.2147/cia.s143632

November 1, 2017Clinical Interventions in AgingOpen Access

Association between apolipoprotein E gene polymorphism and mild cognitive impairment: a meta-analysis

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Why the study?

Is apolipoprotein E (ApoE) gene polymorphism associated with mild cognitive impairment susceptibility?

Structured PICO

Is apolipoprotein E (ApoE) gene polymorphism associated with mild cognitive impairment susceptibility?

P

Population

5,709 subjects (2,004 cases with mild cognitive impairment and 3,705 controls) from 18 case-control studies.

I

Intervention

Apolipoprotein E (ApoE) gene polymorphism (specifically ε4 allele and various genotypes)

C

Comparator

Reference ApoE genotypes (e.g., ε3 allele, ε3/ε3 genotype)

O

Outcome

Mild cognitive impairment (MCI) susceptibility

The ApoE ε4 allele is significantly associated with an increased risk of mild cognitive impairment, whereas the ε2/ε3 genotype may offer slight protection.

Implication

ApoE genotyping may refine MCI risk stratification in older adults; confirms genetic associations but leaves clinical utility and interventions open.

Abstract

A number of published case–control studies reported that the apolipoprotein E (ApoE) gene polymorphism was associated with the mild cognitive impairment (MCI). However, previous reports still remain conflicting. To estimate the association between ApoE polymorphism and MCI susceptibility, we searched the electronic databases including PubMed, Wanfang, CNKI (China National Knowledge Infrastructure), VIP, and EMBASE to retrieve all available studies. A total of 18 studies with 2,004 cases and 3,705 controls were included in this meta-analysis. The pooled analysis based on selected studies showed that statistically significant risk association was found between ApoE gene polymorphism and MCI in overall population ( ε 4 vs ε 3: odds ratio [OR] =2.38, 95% confidence interval [CI]: 2.11–2.68; ε 4/ ε 4 vs ε 3/ ε 3: OR =4.45, 95% CI: 3.06–6.48; ε 2/ ε 4 vs ε 3/ ε 3: OR =2.57, 95% CI: 1.77–3.73; ε 3/ ε 4 vs ε 3/ ε 3: OR =2.31, 95% CI: 1.99–2.69). However, no significant association was detected in two genetic models: ε 2 versus ε 3 (OR =0.90, 95% CI: 0.77–1.05) and ε 2/ ε 2 versus ε 3/ ε 3 (OR =0.91, 95% CI: 0.50–1.65). Furthermore, ApoE ε 2/ ε 3 genotype provided a slight protection for MCI in overall population ( ε 2/ ε 3 vs ε3/ε3: OR =0.80, 95% CI: 0.66–0.97). In the stratified analysis based on ethnicity, similar results were also observed in Chinese population (significant risk: ε 4 vs ε 3: OR =2.52, 95% CI: 2.19–2.90; ε 4/ ε 4 vs ε 3/ ε 3: OR =5.45, 95% CI: 3.41–8.70; ε 2/ ε 4 vs ε 3/ ε 3: OR =2.59, 95% CI: 1.74–3.86; ε 3/ ε 4 vs ε 3/ ε 3: OR =2.34, 95% CI: 1.97–2.79; slight protection: ε 2/ ε 3 vs ε 3/ ε 3: OR =0.79, 95% CI: 0.64–0.98; no association: ε 2 vs ε 3: OR =0.92, 95% CI: 0.78–1.09; and ε 2/ ε 2 vs ε 3/ ε 3: OR =1.04, 95% CI: 0.55–1.99). In summary, this meta-analysis of 5,709 subjects suggested that ApoE ε 4 allele was associated with an increased risk of MCI. In addition, ApoE ε 2/ ε 3 genotype provided a slight protection for MCI.