ApoE polymorphisms and diarrheal outcomes in Brazilian shanty town children

Oriá, Reinaldo B.; Patrick, Peter D.; Oriá, Mônica Oliveira Batista; Lorntz, Breyette; Thompson, M. R.; Azevedo, Orleâncio Gomes Ripardo de; Lôbo, Raimundo Nonato Braga; Pinkerton, Relana; Guerrant, Richard L.; Lima, Aldo A. M.

doi:10.1590/s0100-879x2010007500003

Cited by 60 publications

(48 citation statements)

References 39 publications

(50 reference statements)

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“…Similar to other reports on the Mexican and Asian populations (Aceves et al, 2006;Al-Dabbagh et al, 2009), the APOE *3 allele had a frequency higher than 90% in this sample, unlike other ethnic groups where the *3 frequency ranges between 45 and 83% (Sconce et al, 2006;Kwon et al, 2010;Oriá et al, 2010).…”

Section: Resultssupporting

confidence: 91%

Genetic contribution of CYP2C9, CYP2C19, and APOE variants in acenocoumarol response

et al. 2013

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ABSTRACT. Oral anticoagulants of the coumarin type have an inconveniently narrow therapeutic window, making their use difficult. In Mexico, genetic variables that participate in the heterogeneity of the therapeutic response remain poorly investigated. With the focus on warfarin, extensive pharmacogenomic studies have been performed, including those on the CYP450 family and APOE. The objective of this study was to determine the contribution of CYP2C9, CYP2C19, and APOE polymorphisms to the variations in response to the doses of acenocoumarol, which is the main anticoagulant prescribed to the Mexican population. The polymerase chain reaction-restriction fragment length polymorphism method was applied to identify *2 and *3 of CYP2C9, *2 of CYP2C19, and APOE variants. The genetic distribution of every polymorphism tested showed high variability when compared with other populations worldwide. Our results showed statistical differences only in the CYP2C19 gene between the *1*1 and *1*2 groups, with effective acenocoumarol doses of 2.56 ± 1.34 mg/day vs 1.35 ± 0.84 mg/day (P = 0.005), respectively. Multiple regression analysis, including patient age and both the CYP2C9 and CYP2C19 genes, showed that these variables explained more than 20% of the dose variations. This is the first report in Mexico searching for the relationship between CYP450 and APOE polymorphisms and the dose requirements of acenocoumarol. Our results suggest that, in the Mexican population, CYP2C19 is more involved in acenocoumarol metabolism than CYP2C9 and APOE. Besides considering the age factor, pharmacogenetic testing for CYP2C19*2 before initiating acenocoumarol treatment could lead to a safer anticoagulation therapy in Mexican patients.

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Section: Resultssupporting

confidence: 91%

Genetic contribution of CYP2C9, CYP2C19, and APOE variants in acenocoumarol response

et al. 2013

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“…2002) and improved neurodevelopmental outcomes in infants with malnutrition (Oria et al. 2007, 2010) or lead exposure (Wright et al. 2003).…”

Section: Discussionmentioning

confidence: 99%

Organizational topology of brain and its relationship to ADHD in adolescents with d‐transposition of the great arteries

et al. 2016

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ObjectiveLittle is currently known about the impact of congenital heart disease (CHD) on the organization of large‐scale brain networks in relation to neurobehavioral outcome. We investigated whether CHD might impact ADHD symptoms via changes in brain structural network topology in a cohort of adolescents with d‐transposition of the great arteries (d‐TGA) repaired with the arterial switch operation in early infancy and referent subjects. We also explored whether these effects might be modified by apolipoprotein E (APOE) genotype, as the APOE ε2 allele has been associated with worse neurodevelopmental outcomes after repair of d‐TGA in infancy.MethodsWe applied graph analysis techniques to diffusion tensor imaging (DTI) data obtained from 47 d‐TGA adolescents and 29 healthy referents to construct measures of structural topology at the global and regional levels. We developed statistical mediation models revealing the respective contributions of d‐TGA, APOE genotype, and structural network topology on ADHD outcome as measured by the Connors ADHD/DSM‐IV Scales (CADS).ResultsChanges in overall network connectivity, integration, and segregation mediated worse ADHD outcomes in d‐TGA patients compared to healthy referents; these changes were predominantly in the left and right intrahemispheric regional subnetworks. Exploratory analysis revealed that network topology also mediated detrimental effects of the APOE ε4 allele but improved neurobehavioral outcomes for the APOE ε2 allele.ConclusionOur results suggest that disruption of organization of large‐scale networks may contribute to neurobehavioral dysfunction in adolescents with CHD and that this effect may interact with APOE genotype.

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“…The first, by Oria et al [38], follows up on an earlier study in which they demonstrated that apolipoprotein (APO)E4, an allele well known to predispose to Alzheimer’s disease and cardiovascular disease, protected the cognitive function of a cohort of Brazilian children with heavy diarrhea burdens. They have now determined that APOE4 also protects against early childhood diarrhea [39]. Figure 4 shows that of the three APOE alleles, children with APOE2 and APOE3 have significantly greater burdens of diarrhea in early childhood compared with children with APOE4.…”

Section: Genetic Determinants Of the Infection–nutrition Cyclementioning

confidence: 99%

Interactions of diarrhea, pneumonia, and malnutrition in childhood

Schlaudecker

Steinhoff

Moore

2011

Current Opinion in Infectious Diseases

105

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Purpose of review This review highlights recent progress toward understanding complex interactions between diarrhea, pneumonia, and undernutrition among children in low-income and middle-income countries. Recent findings New studies parallel earlier reports that diarrhea and pneumonia impair children’s growth and that underlying malnutrition is a major risk factor for these conditions. Episodes of diarrhea may predispose to pneumonia in undernourished children. Additional studies support breastfeeding and micronutrient supplementation for the prevention and control of diarrhea and pneumonia. Malnutrition may partially account for the reduced efficacy of oral rotavirus vaccines in low-income countries. Immunization of pregnant women against influenza also appears to reduce intrauterine growth retardation. Immunization of infants against Streptococcus pneumoniae may improve their growth. New genetic studies indicate that polymorphisms in apolipoprotein E or the leptin receptor modulate children’s risk for diarrhea and Entamoeba histolytica infection, respectively, thereby linking two genes important for lipid metabolism to enteric infections. Summary Significant advances have been made in understanding the vicious cycle of malnutrition, diarrhea, and pneumonia in developing countries. Future challenges will be to translate this progress into effective and widely accessible public health measures.

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ApoE polymorphisms and diarrheal outcomes in Brazilian shanty town children

Cited by 60 publications

References 39 publications

Genetic contribution of CYP2C9, CYP2C19, and APOE variants in acenocoumarol response

Genetic contribution of CYP2C9, CYP2C19, and APOE variants in acenocoumarol response

Organizational topology of brain and its relationship to ADHD in adolescents with d‐transposition of the great arteries

Interactions of diarrhea, pneumonia, and malnutrition in childhood

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