Myxovirus resistance, osteopontin and suppressor of cytokine signaling 3 polymorphisms predict hepatitis C virus therapy response in an admixed patient population: comparison with IL28B

OBJECTIVES: Suppressor of cytokine signaling 3, myxovirus resistance protein and osteopontin gene polymorphisms may influence the therapeutic response in patients with chronic hepatitis C, and an association with IL28 might increase the power to predict sustained virologic response. Our aims were to evaluate the association between myxovirus resistance protein, osteopontin and suppressor of cytokine signaling 3 gene polymorphisms in combination with IL28B and to assess the therapy response in hepatitis C patients treated with pegylated-interferon plus ribavirin. METHOD: Myxovirus resistance protein, osteopontin, suppressor of cytokine signaling 3 and IL28B polymorphisms were analyzed by PCR-restriction fragment length polymorphism, direct sequencing and real-time PCR. Ancestry was determined using genetic markers. RESULTS: We analyzed 181 individuals, including 52 who were sustained virologic responders. The protective genotype frequencies among the sustained virologic response group were as follows: the G/G suppressor of cytokine signaling 3 (rs4969170) (62.2%); T/T osteopontin (rs2853744) (60%); T/T osteopontin (rs11730582) (64.3%); and the G/T myxovirus resistance protein (rs2071430) genotype (54%). The patients who had ≥3 of the protective genotypes from the myxovirus resistance protein, the suppressor of cytokine signaling 3 and osteopontin had a greater than 90% probability of achieving a sustained response (p<0.0001). The C/C IL28B genotype was present in 58.8% of the subjects in this group. The sustained virological response rates increased to 85.7% and 91.7% by analyzing C/C IL28B with the T/T osteopontin genotype at rs11730582 and the G/G suppressor of cytokine signaling 3 genotype, respectively. Genetic ancestry analysis revealed an admixed population. CONCLUSION: Hepatitis C genotype 1 patients who were responders to interferon-based therapy had a high frequency of multiple protective polymorphisms in the myxovirus ...

Ancestralidade Genômica, nível socioeconômico e vulnerabilidade ao HIV/aids na Bahia, Brasil / Genomic Ancestry, socioeconomic status and vulnerability to HIV/AIDS in Bahia, Brazil

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.

Ancestry informative markers and complete blood count parameters in Brazilian blood donors / Marcadores informativos de ancestralidade e parâmetros no hemograma de doadores de sangue brasileiros

A complete blood count is very useful in clinical diagnoses when reference ranges are well established for the population. Complete blood counts and allele frequencies of Ancestry Informative Markers (AIMs) were analyzed in Brazilians with the aim of characterizing the hematological values of an admixed population. Positive associations were observed between gender and neutrophils, monocytes, eosinophils, erythrocytes, hemoglobin, hematocrit, MCV, MCHC and platelet counts. No significant differences were found for age, alcohol consumption, educational status, ethnicity, smoking in respect to the complete blood count values. In general, men had higher red blood cell values, while women had higher values for white blood cells and platelets. The study of the population was highly heterogeneous with mean proportions (± SE) of African, European and Amerindian ancestry being 49.0 ± 3.0 percent, 44.0 ± 9.0 percent and 7.0 ± 9.0 percent, respectively. Amerindian ancestry showed limited contribution to the makeup of the population, but estimated ancestral proportions were statistically significant (r = 0.9838; P<0.001). These hematologic values are similar to Afro-Americans, another admixed population.

O hemograma é muito útil no diagnóstico quando o intervalo de referência é adequadamente estabelecido para população. Com o objetivo de verificar os valores hematológicos em população heterogênea foi analisado o hemograma e frequências alélica de marcadores informativos de ancestralidade de brasileiros. Foi observada associação positiva entre sexo e os valores de neutrófilos, monócitos, eosinófilos, eritrócitos, hemoglobina, hematócrito, MCV, MCHC e plaquetas (IC 95 por cento; P<0,05). E não houve diferenças entre idade, consumo de álcool, nível educacional, etnia, tabagismo e os valores do hemograma (IC 95 por cento; P>0,05). Os homens apresentaram valores maiores no eritrograma, enquanto no leucograma e plaquetograma foram as mulheres. Foi observado também que a população é altamente heterogênea e as médias proporcionais (±DP) de ancestralidade Africana, Europeia e Ameríndia estimada foram: 49,0 ± 3,0 por cento, 44,0 ± 9,0 por cento e 7,0 ± 9,0 por cento, respectivamente. A contribuição ancestral ameríndia se demonstrou pequena, mas a estimativa de proporções ancestrais foi estatisticamente significante (r = 0,9838; P<0,001). Os valores hematológicos aqui descritos são parecidos com os descritos em negros americanos, outra população heterogênea.

Microsatellite studies on an isolated population of African descent in the Brazilian state of Bahia

The African descent population of the Bananal community in the Brazilian state of Bahia (BA) was characterized as a genetic isolate and analyzed for some short tandem repeat (STR) microsatellite autosomic polymorphic loci (CSF1PO, TH01, TPOX, F13A1, FESFPS and vWA). These genetic variants were further compared to data obtained from an urban sample from the town of Jequié (BA) regarding demographic and anthropogenetic aspects. The Bananal sample comprised 32 unrelated individuals whereas Jequié was represented by 76 individuals. The Bananal Negroid Phenotypic Index (NPI) was 0.98 and the Negroid Cultural Index (NCI) 0.24. Consanguineous marriages occurred at a frequency of 34.61 percent and the F value was 0.0126. All six loci studied were in Hardy-Weinberg Equilibrium (p > 0.05). The genotypic and allele frequencies of the CSF1PO and vWA loci were similar. In the Bananal population the genic diversity of the THO1 locus was 66.8 percent and that of the F13A1 locus was 83.7 percent. The estimated ethnic racial admixture was 81 percent African and 19 percent Amerindian. The multiple correlation coefficient (R²) indicated adequate adaptation (99 percent). Total genetic variation for the six loci was 82.9 percent with an index of 6.7 percent for population subdivision (G ST' = 0.067). Anthropologic data and results obtained from the allele frequencies of the loci studied are indicative of a genetic isolate in Bananal, reminiscent of the a 'quilombo community' (i.e. one founded by run away slaves).