Association of apolipoprotein E genetic variation in Alzheimer's disease in Indian population: a meta-analysis.

BACKGROUND: Dementia is an age-related disorder associated with elderly population, resulting from interaction of lifestyle risk factors with genetic, vascular, and other risk factors to affect risk of disease. Alzheimer's disease (AD) is the most common form of dementia, estimated to be affecting 4.4% of the population older than 65 years of age. Apolipoprotein E (ApoE) ε4 allele is a known genetic risk factor for AD, which not only predisposes and influences the severity of pathological changes in the brain, thereby modifying the age at onset, but also promotes cognitive decline early in nondemented older people.

OBJECTIVES: To review the published evidence on ApoE polymorphism with the susceptibility to AD and frequency of ApoE ε4 genotype (ε4/-) and homozygotes (ε4/4) among patients diagnosed with AD as compared to controls in Indian Population.

MATERIALS AND METHODS: In the present study, MEDLINE was reviewed for articles published till June 2013 supplemented by citation analysis from retrieved articles to select case-control studies. A meta-analysis was performed to demonstrate the association of ApoE gene with vascular dementia by random effects to demonstrate models. The association was assessed by odds ratio (OR) with 95% confidence intervals (CIs).

STUDY SELECTION: Case-control studies, using clinical criteria for AD with ApoE polymorphism determined for allele and genotype in both cases and controls.

STATISTICAL ANALYSIS: A meta-analysis was performed to demonstrate the association of ApoE gene with AD by random effects to demonstrate models. The association was assessed by OR with 95% CIs. We also looked for publication bias and performed sensitivity analysis to investigate the influence of each individual study.

RESULTS: A total of 7 studies representing data from 417 patients with AD and 651 controls in the Indian population were eligible. The ApoE ε2/4, ε3/4, and ε4/4 genotypes (OR = 3.93, 95% CI: 1.60-9.68; OR = 4.18, 95% CI: 2.54-6.87; OR = 4.81, 95% CI: 1.95-11.86, respectively) as well as ApoE ε4 allele (OR = 5.90, 95% CI: 3.44-10.13) were associated with an increased risk of AD, whereas ApoE ε2/3, ε3/3 genotypes (OR = 0.52, 95% CI: 0.32-0.83; OR = 0.28, 95% CI: 0.19-0.42), and ApoE ε3 allele (OR = 0.29, 95% CI: 0.17-0.50) were found to be marginally significant protective factors for AD. There was no significant difference in ApoE ε2/2 genotype and ApoE ε2 allele frequency (OR = 0.42; 95% CI: 0.11-1.68; OR = 0.69, 95% CI: 0.37-1.31, respectively) in patients with AD and controls.

CONCLUSIONS: These results indicate that all genotypes of ApoE ε4 allele, that is, ε2/4, ε3/4, and ε4/4, are associated with an increased risk of AD, whereas ApoE ε2/2, ε2/3, and ε3/3 are protective for AD.