Amerindian Genetic Ancestry Protects against Alzheimers Disease

Benedet, Andréa Lessa; Moraes, Clayton Franco; Camargos, Einstein Francisco; Oliveira, Larissa F.; Souza, Vinícius Carolino; Lins, Tulio Cesar de Lima; Henriques, Adriane Dallanora; Carmo, Dayanne G.S.; Machado-Silva, Wilcelly; Araújo, Carla Nunes; Córdova, Cláudio; Pereira, Rinaldo Wellerson; Nóbrega, Otávio de Tolêdo

doi:10.1159/000339672

Cited by 25 publications

(34 citation statements)

References 34 publications

(33 reference statements)

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“…Apart from the well-characterized contribution of the classic susceptibility genes to the etiology of AD, a body of recent evidence accounts for the overall genetic heritage as an additional genetic risk factor, as observed in the highly admixed Brazilian population [23,45]. However, our stratified analyses did not detect an interaction between either the ApoE ε4 allele or the degree of Amerindian ancestry and the genotypes of IL10 , rendering the apolipoprotein alleles and Native American heritage as potential confounders rather than effect-modifying variables.…”

Section: Discussionmentioning

confidence: 99%

“…The present study represents an analysis of data from an ongoing initiative for cognitive assessments in Brasília, Brazil [23], whose methods are reproduced below. This city (∼2.6 million inhabitants) has the important feature of having been planned and constructed to bring the administrative capital from the coast to the midwest of Brazil, giving rise to a migration process over the last 50 years.…”

Section: Methodsmentioning

confidence: 99%

“…The concentrations used and the sequence of all primers are available upon request. Genetic ancestry estimates were determined for each subject exactly as described previously [23]. …”

Section: Methodsmentioning

confidence: 99%

“…This latter analysis was confirmed with the χ 2 test. Individual genetic ancestry was estimated with an algorithm based on maximum likelihood estimation [36] and determined exactly as described previously [23]. p values were rendered significant following the Bonferroni correction for multiple genotypic tests (α = 0.005).…”

Section: Methodsmentioning

confidence: 99%

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Cytokine Gene Polymorphisms and Alzheimer's Disease in Brazil

Moraes

Benedet

Souza

et al. 2013

Neuroimmunomodulation

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Background: Single-nucleotide polymorphisms in genes encoding immunological mediators can affect the biological activity of these molecules by regulating transcription, translation, or secretion, modulating the genetic risk of inflammatory damage in Alzheimer's disease (AD). Nonetheless, the Brazilian contingent is highly admixed, and few association trials performed herein with AD patients have considered genetic ancestry estimates as co-variables when investigating markers for this complex trait. Methods: We analyzed polymorphisms in 10 inflammatory genes and compared the genotype distribution across outpatients with late-onset AD and noncognitively impaired subjects from Midwest Brazil under a strict criterion, and controlling for ancestry heritage and ApoE genotype. Results: Our findings show an almost 40% lower chance of AD (p = 0.004) among homozygotes of the IL10 -1082A allele (rs1800896). Dichotomization to ApoE and mean ancestry levels did not affect protection, except among those with greater European or minor African heritage. Conclusion: The IL10 locus seems to affect the onset of AD in a context sensitive to the genetic ancestry of Brazilian older adults.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…The concentrations used and the sequence of all primers are available upon request. Genetic ancestry estimates were determined for each subject exactly as described previously [23]. …”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Cytokine Gene Polymorphisms and Alzheimer's Disease in Brazil

Moraes

Benedet

Souza

et al. 2013

Neuroimmunomodulation

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“…Interestingly, Amerindian ancestry also affects the frequency of other diseases. For instance, Amerindian ancestry is associated with an increased frequency of lupus erythematosus (Alarcon-Riquelme et al, 2016), but Amerindians have a lower risk of contracting leprosy, psoriasis, or Alzheimer's disease (Benedet et al, 2012;Garcia et al, 2013;Parisi, Symmons, Griffiths, & Ashcroft, 2013). Also, they differ from Europeans in 18…”

Section: Prevalence Of Vitiligo In Brazil-a Population Surveymentioning

confidence: 99%

Prevalence of vitiligo in Brazil—A population survey

Castro

Miot

2018

Pigment Cell Melanoma Res

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Amerindian ancestry and extended longevity in Nicoya, Costa Rica

Azofeifa

Ruiz-Narváez

Leal

et al. 2017

American J Hum Biol

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Objectives: The aim of this study was to address the hypothesis that Amerindian ancestry is associated with extended longevity in the admixed population of Nicoya, Costa Rica. The Nicoya Peninsula of Costa Rica has been considered a "longevity island," particularly for males. Methods:We estimated Amerindian ancestry using 464 ancestral informative markers in 20 old Nicoyans aged 99 years, and 20 younger Nicoyans (60-65 years). We used logistic regression to estimate odds ratio (OR) and 95% confidence interval (CI) of the association of Amerindian ancestry and longevity.Results: Older Nicoyans had higher Amerindian ancestry compared to younger Nicoyans (43.3% vs 36.0%, P 5 .04). Each 10% increase of Amerindian ancestry was associated with more than twice the odds of being long-lived (OR 5 2.32, 95% CI 5 1.03-5.25).Conclusions and Implications: To our knowledge, this is the first time that ancestry is implicated as a likely determinant of extended longevity. Amerindian-specific alleles may protect against early mortality. The identification of these protective alleles should be the focus of future studies.

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Amerindian Genetic Ancestry Protects against Alzheimers Disease

Cited by 25 publications

References 34 publications

Cytokine Gene Polymorphisms and Alzheimer's Disease in Brazil

Cytokine Gene Polymorphisms and Alzheimer's Disease in Brazil

Prevalence of vitiligo in Brazil—A population survey

Amerindian ancestry and extended longevity in Nicoya, Costa Rica

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Amerindian Genetic Ancestry Protects against Alzheimers Disease

Cited by 25 publications

References 34 publications

Cytokine Gene Polymorphisms and Alzheimer's Disease in Brazil

Cytokine Gene Polymorphisms and Alzheimer's Disease in Brazil

Prevalence of vitiligo in Brazil—A population survey

Amerindian ancestry and extended longevity in Nicoya, Costa Rica

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Amerindian Genetic Ancestry Protects against Alzheimers Disease