ABSTRACT
Gastric cancer (GC) is the fifth most common type of cancer worldwide with high incidences in Asia, Central, and South American countries. This patchy distribution means that GC studies are neglected by large research centers from developed countries. The need for further understanding of this complex disease, including the local importance of epidemiological factors and the rich ancestral admixture found in Brazil, stimulated the implementation of the GE4GAC project. GE4GAC aims to embrace epidemiological, clinical, molecular and microbiological data from Brazilian controls and patients with malignant and pre-malignant gastric disease. In this letter, we summarize the main goals of the project, including subject and sample accrual and current findings
Subject(s)
Humans , Adult , Middle Aged , Aged , Stomach Neoplasms/epidemiology , Brazil , Adenocarcinoma , ProjectsABSTRACT
Abstract:CYP2C9, CYP2C19 and CYP2D6 metabolize around 40 % of drugs and their genes vary across populations. The Costa Rican population has a trihybrid ancestry and its key geographic location turns it into a suitable scenario to evaluate interethnic differences across populations. This study aims to describe the diversity of CYP2C9, CYP2C19 and CYP2D6 polymorphisms in Costa Rican populations in the context of their ancestry. A total of 448 healthy individuals were included in the study: Bribri (n= 47), Cabécar (n= 27), Maleku (n= 16), Guaymí (n= 30), Huetar (n= 48), Chorotega (n= 41), Admixed/Mestizos from the Central Valley/Guanacaste (n= 189), and Afro-Caribbeans (n= 50) from Limón. CYP2C9 (alleles *2, *3, *6) and CYP2C19 (*2, *3, *4, *5, *17) genotypes were determined by Real-Time PCR. African, European and Native American ancestry were inferred using 87 ancestry informative markers. The frequency of the decreased activity allele CYP2C9*2 is lower in the self-reported Amerindian groups compared to the admixed population, and the highest frequencies of CYP2C19*2 (null activity) and the CYP2C19*17 (increased activity) were found in the self-reported AfroCaribbean population. Moreover, a frequency of 0.7 % CYP2C9 gPMs in the Admixed population and a variable frequency of CYP2C19 gUMs (0.0-32.6 %, more prevalent in Afro-Caribbeans) in Costa Rican populations, was found. Finally, the following alleles were positively correlated with genomic African ancestry and negatively correlated with genomic Native American ancestry: CYP2D6*5 (null activity), CYP2D6*17 (decreased activity), CYP2D6*29 (decreased activity) and CYP2C19*17 (increased activity). No correlation for CYP2C9 polymorphisms and genomic ancestry was found. Further studies assessing the CYP2C9 and CYP2C19 sequence in these populations, preferentially by sequencing these genes, are warranted. Rev. Biol. Trop. 64 (3): 1067-1076. Epub 2016 September 01.
ResumenCYP2C9, CYP2C19 y CYP2D6 metabolizan aproximadamente el 40 % de los fármacos y los genes que las codifican varían en las distintas poblaciones humanas. La población costarricense posee ancestría trihíbrida y su posición geográfica estratégica la convierten en un escenario idóneo para evaluar la variabilidad interétnica en sus poblaciones multiétnicas. El presente estudio tiene como objetivo describir la diversidad de los polimorfismos CYP2C9, CYP2C19 y CYP2D6 en las poblaciones costarricenses en el contexto de su ancestría. Un total de 448 individuos sanos fueron incluidos: Bribri (n= 47), Cabécar (n= 27), Maleku (n= 16), Guaymí (n= 30), Huetar (n= 48), Chorotega (n= 41), mestizos del Valle Central y Guanacaste (n= 189) y afrocaribeños de Limón (n= 50). Los genotipos CYP2C9 (alelos *2, *3, *6) y CYP2C19 (*2, *3, *4, *5 y *17) fueron determinados mediante PCR tiempo real. Las ancestrías africana, europea y nativa americana fueron inferidas usando 87 marcadores informativos de ancestría. La frecuencia del alelo de actividad disminuida CYP2C9*2 fue menor en los grupos autodefinidos de amerindios que en la población mestiza y las frecuencias más altas de CYP2C19*2 (actividad nula) y CYP2C19*17 (actividad incrementada) se encontraron en la población autodefinida afrocaribeña. Asimismo, se encontró una frecuencia de gPMs CYP2C9 de 0.7 % en la población mestiza y una frecuencia variable de gUMs CYP2C19 (0.0 a 32.6 %, más prevalente en afrocaribeños) en las poblaciones costarricenses. Por último, los siguientes alelos fueron positivamente correlacionados con la ancestría africana y negativamente con la ancestría nativa americana: CYP2D6*5 (actividad nula), CYP2D6*17, CYP2D6*29 (ambos de actividad disminuida) y CYP2C19*17 (actividad incrementada). No se encontró correlación entre los polimorfismos CYP2C9 y la ancestría. Se requieren estudios posteriores que evalúen la secuencia de CYP2C9 y CYP2C19 en estas poblaciones, preferiblemente mediante la secuenciación de estos genes.
Subject(s)
Humans , Cytochrome P-450 CYP2D6/genetics , Black People/genetics , American Indian or Alaska Native/genetics , Asian People/genetics , Cytochrome P-450 CYP2C9/genetics , Cytochrome P-450 CYP2C19/genetics , Polymorphism, Genetic , Reference Values , Costa Rica/ethnology , Alleles , Self Report , Real-Time Polymerase Chain Reaction , Gene Frequency , GenotypeABSTRACT
O curso clínico da infecção pelo HIV é determinado por complexas interações entre características virais e o hospedeiro. Variações no hospedeiro, a exemplo das mutações CCR5Δ32 e CCR264I, são importantes para a vulnerabilidade e progressão do HIV/aids. Atualmente, observa-se um aumento do número de casos da infecção entre os segmentos da sociedade com menor nível de escolaridade e pior condição socioeconômica. Com o objetivo de estimar a ancestralidade e verificar a sua associação com renda, escolaridade vulnerabilidade e progressão ao HIV/aids foram analisados 517 indivíduos infectados pelo HIV-1, sendo 289 homens e 224 mulheres. Os pacientes foram classificados segundo a ancestralidade genômica avaliada por 10 AIMs e pela vulnerabilidade e progressão ao HIV/aids através das mutações CCR5Δ32 e CCR264I. Os indivíduos infectados pelo HIV-1 apresentaram contribuição africana de 47 por cento. As mutações CCR5Δ32 e CCR264I foram mais frequentes nos indivíduos brancos (3 por cento) e negros (18 por cento) respectivamente, e essas mutações mostraram frequência mais elevada nos tipicamente progressores (TP), quando comparados com os rapidamente progressores (RP) para aids. Não foi encontrada associação entre ancestralidade e vulnerabilidade ao HIV na análise para o grau de instrução. A pauperização da infecção pelo HIV-1 nessa população foi confirmada pela relação inversa entre renda e ancestralidade africana, pois quanto menor a renda maior a ancestralidade africana. Os resultados deste estudo sugerem associação entre as condições socioeconômicas e vulnerabilidade ao HIV/aids da população afrodescendente.
The clinical course of HIV infection is determined by complex/ interactions between viral and host's characteristics./ Host variations, such as CCR5δ32 and CCR264I mutations, are important/ to vulnerability and progression of HIV/AIDS./ Currently, the number of cases among patients with lower educational level and lower social and economic status is/ increasing./ Aiming to/ estimate the ancestry and verify its association with income,/ education, vulnerability and progression of HIV/AIDS, 517 individuals infected with HIV-1 were studied (55.9 percent men and 43.3 percent women). The/ patients were/ classified according to/ genomic ancestry evaluated by 10 AIMs and by vulnerability and/ progression of HIV/AIDS through CCR5δ32 and CCR264I mutations./ The/ individuals infected with HIV-1 showed 47 percent of African contribution./ CCR5δ32 and CCR264I mutations were more frequent in white/ (3 percent) and black (18 percent) individuals, respectively, and these same mutations/ showed higher frequency in the typically progressive HIV-infected individuals (TP), when compared to the rapidly progressive (RP)./ There was no association between ancestry and/ vulnerability to HIV in the analysis of level of education./ The pauperization of the HIV-1 infection in this population was confirmed by/ the inverse relationship between income and African ancestry, because the lower/ the income, the greater the African ancestry./ The results suggest that there is an association between socioeconomic status and vulnerability to HIV/AIDS in the Afro-descendant population.