The complex interaction between APOE promoter and AD: an Italian case–control study

Bizzarro, Alessandra; Seripa, Davide; Acciarri, Adele; Matera, Maria G.; Tiziano, Francesco Danilo; Brahe, Christina; Masullo, Carlo

doi:10.1038/ejhg.2008.263

Cited by 36 publications

(37 citation statements)

References 41 publications

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“…The frequencies of APOE genotypic and allelic frequencies analyzed here were similar to those reported in other samples [15,19,31]. Our results did not show associations between cognitive performance and any of APOE polymorphisms analyzed here, except for rs429358.…”

Section: Discussionsupporting

confidence: 90%

Influence of multiple APOE genetic variants on cognitive function in a cohort of older men – results from the Normative Aging Study

et al. 2014

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BackgroundAPOE is the biomarker with the greatest known influence on cognitive function; however, the effect of complex haplotypes involving polymorphisms rs449647, rs405509, rs440446, rs429358 and rs7412 has never been studied in older populations.MethodsWe evaluated APOE polymorphisms using multiplex PCR for genotyping and Mini-Mental State Examination (MMSE) to evaluate cognitive function in 819 individuals from VA Normative Aging Study.ResultsCombinatorial analysis of all polymorphisms and individual analysis of polymorphisms rs449647, rs405509, rs440446 and rs7412 did not show any association with cognitive performance. Polymorphism rs429358 was associated with better cognitive performance (odds of MMSE ≤ 25 = 0.63, 95% CI 0.42-0.95; p = 0.03) in the oldest subsample (5th quintile of age) (odds of MMSE ≤ 25 = 0.34; 95% CI 0.13-0.86; p = 0.02). APOE allele ε4 was also associated with better cognitive performance (odds of MMSE ≤ 25 = 0.61, 95% CI 0.40-0.94; p = 0.02), also in the oldest subsample (odds of MMSE ≤ 25 = 0.35, 95% CI 0.14-0.90; p = 0.03).ConclusionsThese results suggest a beneficial effect of polymorphism rs429358 in the oldest men.Electronic supplementary materialThe online version of this article (doi:10.1186/s12888-014-0223-x) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 90%

Influence of multiple APOE genetic variants on cognitive function in a cohort of older men – results from the Normative Aging Study

et al. 2014

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“…The apoE4/E4 proinflammatory genotype was present in 2.9 per cent of the Tsimane sample whereas the at-risk genotype (GG) of the SNP in the promoter region (rs405509), which has also been associated with Alzheimer’s disease (Bizzarro et al 2009), was found in 6.4 per cent of the Tsimane (see Table 3). …”

Section: Resultsmentioning

confidence: 99%

Inflammatory Gene Variants in the Tsimane, an Indigenous Bolivian Population with a High Infectious Load

Vasunilashorn

Finch

Crimmins

et al. 2011

Biodemography and Social Biology

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The Tsimane of lowland Bolivia are an indigenous forager-farmer population living under conditions resembling pre-industrial European populations, with high infectious morbidity, high infection and inflammation, and shortened life expectancy. Analysis of 917 persons ages 5 to 60+ showed that allele frequencies of 9 SNPs examined in the apolipoprotein E (apoE), C-reactive protein (CRP), and interleukin-6 (IL-6) genes differed from some European, African, and north Asian-derived populations. The apoE2 allele was absent, whereas four SNPs related to CRP and IL-6 were monomorphic: CRP (rs1800947, rs3093061, and rs3093062) and IL-6 (rs1800795). No significant differences in apoE, CRP, and IL-6 variants across age were found CRP levels were higher in carriers of two CRP proinflammatory SNPs, whereas they were lower in carriers of apoE4. Taken together, the evidence for (1) different allele frequencies between the Tsimane and other populations and (2) the correlations of CRP and apoE alleles with blood CRP may suggest that these variants are under selection in response to a high infection environment.

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“…A more recent study reported both TT and GG genotypes of rs405509 with higher odds ratios for AD compared with the GT group in the APOE ɛ4 carriers. However, in ɛ3/ɛ3 carriers, both TT and GG showed lower frequencies than GT in patients with AD . In another study, the rs405509 T‐APOEɛ4 haplotype could increase the risk of AD .…”

Section: Introductionmentioning

confidence: 90%

Is there a significant interaction effect between apolipoprotein E rs405509 T/T and ε4 genotypes on cognitive impairment and gray matter volume?

Zhang

et al. 2016

Euro J of Neurology

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Background Evidence demonstrates that the T allele of the single-nucleotide polymorphism rs405509 in the apolipoprotein E (APOE) promoter is a risk factor for Alzheimer’s disease (AD). However, it is unknown whether rs405509 T allele synergizes to the APOE ε4 allele in influencing cognition and brain structure. Methods We analyzed the interaction of the rs405509 T allele and the APOE ε4 allele on cognitive ability and brain gray matter volume (GMV) among the elderly people. The subjects were grouped into four groups according to APOE and rs405509 genotypes. Results Significant interactions were found between rs405509 and APOE on general mental status, memory and attention. Analysis of the whole brain gray matter showed a significantly positive interaction between rs405509 and APOE on the right inferior temporal gyrus and the right fusiform gyrus (alphasim correction p<0.001).Additionally, there was a significant relationship between cognitive ability and GMV. Conclusions The data indicates that the APOE rs405509 T homozygote modulates effect of APOE ε4 on both cognitive performance and brain gray matter structure.

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The complex interaction between APOE promoter and AD: an Italian case–control study

Cited by 36 publications

References 41 publications

Influence of multiple APOE genetic variants on cognitive function in a cohort of older men – results from the Normative Aging Study

Influence of multiple APOE genetic variants on cognitive function in a cohort of older men – results from the Normative Aging Study

Inflammatory Gene Variants in the Tsimane, an Indigenous Bolivian Population with a High Infectious Load

Is there a significant interaction effect between apolipoprotein E rs405509 T/T and ε4 genotypes on cognitive impairment and gray matter volume?

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