Factors associated with potentially inappropriate medications in elderly with multiple myeloma.

INTRODUCTION: Elderly with cancer often have multimorbidity, which determines a higher risk of polypharmacy. This is related to negative clinical results such as adverse drug reaction and emergence service visits. Furthermore, polypharmacy increases the risk of using potentially inappropriate medications. OBJECTIVE: To evaluate the use of potentially inappropriate medication in elderly with multiple myeloma and associated factors. METHODS: The study was conducted with older adults with multiple myeloma treated at outpatient oncology and hematology services in a southeastern Brazilian capital. Potentially inappropriate medications were classified using the American Geriatric Society/Beers 2019 Criteria. Variables were described using frequency and proportions, performing multiple logistic regression to identify factors associated with the use of potentially inappropriate medications. RESULTS: One hundred fifty-three older adults with multiple myeloma were included, with a median age of 70.9 years. The median number of medications was 8, and 63% of patients used polypharmacy. More than half (54%) of the patients used potentially inappropriate medications, and proton pump inhibitors (46%) and benzodiazepines (8%) were the most employed therapeutic classes. Older adults who used potentially inappropriate medications differed from those who did not use them in the following characteristics: income up to three minimum wages, higher schooling level, private service, multimorbidity, hypertension, cardiovascular disease, chronic kidney disease, depression, adverse event, and polypharmacy. Higher schooling levels and polypharmacy were independently associated with the use of potentially inappropriate medications in the multivariate analysis. CONCLUSION: Potentially inappropriate medication use was high in patients with multiple myeloma studied. The use of polypharmacy and higher schooling levels were independently and positively associated with the use of potentially inappropriate medications.

Adherence to thalidomide in patients with multiple myeloma: A cross-sectional study in a Brazilian metropolis.

PURPOSE: The treatment of multiple myeloma (MM) has advanced with the introduction of immunomodulators (IMiDS). Thalidomide is the IMiD available in Brazil with free access to MM patients. Adherence to treatment with IMiDs is essential for a successful therapy. The study proposed to describe adherence to thalidomide treatment in patients diagnosed with MM in onco-hematological outpatient clinics. METHODS: This is a cross-sectional study with patients over 18 years of age diagnosed with MM undergoing thalidomide treatment. Adherence was measured by the Proportion of Days Covered (PDC), which is an indirect method of measuring adherence that uses database-related medication dispensing information. Patients with PDC ≥90 were classified as adherent. The association between adherence and independent variables was assessed in univariate and multivariate analyses using logistic regression. RESULTS: A total of 65 patients with a median age of 62.6 years were identified. The median PDC was 93.7%. The frequency of adherence to thalidomide was 56.9%. Adherence to thalidomide showed a negative association with hospitalization in the last 12 months (OR = 0.202; 95% CI = 0.060-0.687) and with higher schooling (OR =0.161; 95% CI = 0.039-0.667) and a positive association with higher income (OR = 5.115; 95% CI = 1.363-19.190). CONCLUSION: Most patients from onco-hematological outpatient clinics in a metropolitan region of southeastern Brazil showed high adherence to thalidomide, which was independently associated with higher income, hospitalization, and higher schooling. More studies are required to understand better the determinants of adherence to thalidomide in the country.

BRCA1 and BRCA2 rearrangements in Brazilian individuals with Hereditary Breast and Ovarian Cancer Syndrome.

Approximately 5-10% of breast cancers are caused by germline mutations in high penetrance predisposition genes. Among these, BRCA1 and BRCA2, which are associated with the Hereditary Breast and Ovarian Cancer (HBOC) syndrome, are the most frequently affected genes. Recent studies confirm that gene rearrangements, especially in BRCA1, are responsible for a significant proportion of mutations in certain populations. In this study we determined the prevalence of BRCA rearrangements in 145 unrelated Brazilian individuals at risk for HBOC syndrome who had not been previously tested for BRCA mutations. Using Multiplex Ligation-dependent Probe Amplification (MLPA) and a specific PCR-based protocol to identify a Portuguese founder BRCA2 mutation, we identified two (1,4%) individuals with germline BRCA1 rearrangements (c.547+240_5193+178del and c.4675+467_5075-990del) and three probands with the c.156_157insAlu founder BRCA2 rearrangement. Furthermore, two families with false positive MLPA results were shown to carry a deleterious point mutation at the probe binding site. This study comprises the largest Brazilian series of HBOC families tested for BRCA1 and BRCA2 rearrangements to date and includes patients from three regions of the country. The overall observed rearrangement frequency of 3.44% indicates that rearrangements are relatively uncommon in the admixed population of Brazil.

A community-based study of mucopolysaccharidosis type VI in Brazil: the influence of founder effect, endogamy and consanguinity.

Mucopolysaccharidosis type VI (MPS VI - Maroteaux-Lamy syndrome) is a globally rare lysosomal storage disease caused by a deficiency of arylsulfatase B. However, in Monte Santo, a poor and isolated rural region in Northeast Brazil with large family sizes and high rates of community endogamy and parental consanguinity (α = 0.00483), 9 living and 4 now deceased individuals in 11 kindreds have been diagnosed with MPS VI, all with the same p.H178L missense founder mutation. A further 33 deceased persons have been identified by family members as exhibiting the disease phenotype. Detailed pedigrees were constructed for the 13 genomically confirmed MPS VI patients, with blood samples collected from 236 unaffected family members to determine the prevalence of the p.H178L mutation. A total of 98 (20.8%) mutant alleles and 374 (79.2%) normal alleles were identified, with 41.5% of the individuals heterozygous for the p.H178L mutation and 58.5% homozygous for the normal allele. A significant number of other family members with a 50 or 25% chance of being heterozygous for the p.H178L mutation were unavailable for testing. The data indicate a compelling case for community-based neonatal screening in conjunction with further initiatives among MPS VI family members to promote genetic education and genetic counselling.

IL28B polymorphisms are markers of therapy response and are influenced by genetic ancestry in chronic hepatitis C patients from an admixed population.

BACKGROUND: IL28B polymorphisms are predictors of therapy response in hepatitis C virus (HCV) patients. We do not know whether they are markers of treatment response in admixed populations or not. AIMS: To determine whether IL28B polymorphisms are predictors of therapy response in patients with HCV from an admixed population and are influenced by genetic ancestry. METHODS: rs12979860 and rs8099917 were genotyped in 222 HCV patients treated with pegylated interferon and ribavirin. Ancestry was determined using genetic markers. RESULTS: IL28B rs12979860 C/C was associated with sustained virological response (SVR), whereas C/T and T/T were associated with failure to therapy (P = 1.12 × 10(-5) ). IL28B rs8099917 T/T was associated with SVR, and G/G and G/T were associated with nonresponse/relapse (NR/R) (P = 8.00 × 10(-3) ). Among HCV genotype 1 patients with C/C genotype, genomic ancestry did not interfere with therapy response. Among patients with rs12979860 T/T genotype, African genetic contribution was greater in the NR/R group (P = 1.51 × 10(-3) ), whereas Amerindian and European genetic ancestry contribution were higher in the SVR group (P = 3.77 × 10(-3) and P = 2.16 × 10(-2) respectively). Among HCV type 1 patients with rs8099917 T/T, African genetic contribution was significantly greater in the NR/R group (P = 5.0 × 10(-3) ); Amerindian and European ancestry genetic contribution were greater in the SVR group. CONCLUSION: IL28B rs12979860 and rs8099917 polymorphisms were predictors of therapy response in HCV genotypes 1, 2 and 3 subjects from an admixed population. Genomic ancestry did not interfere with response to therapy in patients with rs12979860 C/C, whereas it interfered in patients with C/T and T/T genotypes. Among HCV genotype 1 rs8099917 T/T patients, genomic ancestry interfered with response to therapy.

Use of fall risk-increasing drugs in older adults with multiple myeloma: A cross-sectional study.

OBJECTIVE: To investigate the use of fall risk-increasing drugs (FRIDs) and associated factors and to assess the use of medicines that induce neuropathy in older adults with multiple myeloma (MM). METHODS: Cross-sectional study with older adults with MM treated at the outpatient oncology and hematology services in a southeastern Brazilian capital. FRIDs were classified according to the Screening Tool of Older Persons Prescription in older adults with high fall risk (STOPPFall). The high risk of falling was defined using the Medication Fall Risk Score scale, and the medicines that induce neuropathy were identified according to Vilholm et al. (2014) and Jones et al. (2019). Univariate and multivariate analyses were performed to verify the association between variables. RESULTS: Approximately 54.2% of the 153 older adults included in the study were female, and the median age was 70.9 years (IQR = 13; min = 60 and max:92). Around 71.3% used FRIDs, and diuretics (25.6%), antidepressants (20.5%), and opioids (19.9%) were the most used. A total of 32.7% had a high risk of falling. Polypharmacy was associated with a higher risk of using FRIDs. Statins used concomitantly with immunomodulators or bortezomib were the most used neuropathyinducing drugs, increasing fourfold the likelihood of reporting peripheral neuropathy. CONCLUSION: The frequency of use of FRIDs is high in older adults with MM and is positively associated with polypharmacy.

Validation of an Instrument for Measuring Adherence to Treatment With Immunomodulators in Patients With Multiple Myeloma.

Background: Validate the Treatment Adherence Measure (TAM) instrument in outpatients with MM concerning construct validity, reliability and the ceiling and floor effects. Methods: This cross-sectional study included patients diagnosed with MM previously treated with an immunomodulator for at least one month, aged 18 or over, and followed-up in the investigated outpatient clinics. Adherence to immunomodulators was measured by TAM. The TAM's reliability was assessed using Cronbach's alpha; The association between adherence and health-related quality of life was investigated to analyze the divergent and convergent construct, measured by the Quality of Life Questionnaire core (QLQ-C30) and the Quality of Life Questionnaire Multiple Myeloma module (QLQ-MY20). The presence of a ceiling or floor effect in the TAM was also analyzed. Results: Eighty-four patients were included in the study, achieving 97.6% adherence. Cronbach's alpha was 0.41, and the hypothesis of convergent construct validity was confirmed, with statistical significance, in contrast to the hypothesis of divergent construct validity. The presence of the ceiling effect in TAM suggested that this instrument does not allow changes to be detected in individuals concerning adherence to IMiDs. Conclusion: TAM instrument did not show satisfactory validity and reliability to measure MM's adherence. MM patients treated at oncohematological outpatient clinics in a metropolitan region of southeastern Brazil showed high adherence to IMiDs.

Use of potentially inappropriate medications and medications of concern in older adults with multiple myeloma / Utilização de medicamentos potencialmente inapropriados e medicamentos que requerem cautela em idosos com mieloma múltiplo

Objetivo: Analisar o uso de medicamentos potencialmente inapropriados (MPIs) e o uso de medicamentos usados em terapia de suporte que requerem cautela em idosos com câncer (MTSRCICs), determinando os fatores associados. Visou-se também determinar a concordância entre os critérios explícitos empregados na identificação de MPI. Metodologia: Estudo transversal com indivíduos com mieloma múltiplo (MM), idade ≥ 60 anos em tratamento ambulatorial. Os MPI foram identificados de acordo com os critérios AGS Beers 2019, PRISCUS 2.0 e o Consenso Brasileiro de Medicamentos Potencialmente Inapropriados (CBMPI). Os MTSRCIC foram definidos de acordo com a National Comprehensive Cancer Network. Os fatores associados ao uso de MPI e MTSRCIC foram identificados por regressão logística múltipla. O grau de concordância entre os três critérios explícitos empregados no estudo foi mensurado pelo coeficiente kappa Cohen. Resultados: As frequências de MPI foram 52,29% (AGS Beers 2019), 62,74% (CBMPI), 65,36% (PRISCUS 2.0) e 52,29% (MTSRCICs). As concordâncias entre AGS Beers 2019 com PRISCUS 2,0 e com CBMPI foram altas, enquanto a concordância entre CBMPI e PRISCUS 2.0 foi excelente. No modelo final de regressão logística polifarmácia foi associada positivamente ao uso de MPI por idosos para os três critérios explícitos utilizados, além de associado à utilização de MTSRCICs. Conclusões: A frequência do uso de MPI e de MTSRCIC foi elevada. A concordância em relação ao uso de MPI entre os critérios AGS Beers 2019, CBMPI e PRISCUS 2.0 foi alta ou excelente. A polifarmácia apresentou associação independente e positiva com uso de MPIs e de MTSRCICs por pacientes idosos com MM. (AU)

Objectives: To analyze the use of potentially inappropriate medications (PIMs) and medications used in supportive therapy that require caution in older adults with cancer, in addition to determining associated factors the agreement between criteria sets used to identify PIMs. Methods: This cross-sectional study included individuals with multiple myeloma aged ≥ 60 years who were undergoing outpatient treatment. PIMs were identified according to American Geriatric Society Beers 2019, PRISCUS 2.0, and Brazilian Consensus on Potentially Inappropriate Medicines criteria. Medications of concern were defined according to National Comprehensive Cancer Network criteria. Factors associated with the use of PIMs and medications of concern were identified using multiple logistic regression. The degree of agreement between the 3 criteria sets was measured using Cohen's kappa coefficient. Results: The frequency of PIM use was 52.29% according to American Geriatric Society Beers criteria, 62.74% according to Brazilian Consensus criteria, and 65.36% according to PRISCUS criteria, while 52.29% of the patients were using medications of concern. Agreement between American Geriatric Society Beers, PRISCUS, and Brazilian Consensus criteria was high, while it was excellent between Brazilian Consensus and PRISCUS criteria. In the final logistic regression model, polypharmacy was associated with PIM use according to each criteria set, as well as the use of medications of concern. Conclusions: The frequency of PIMs and medications of concern was high. Agreement about PIM use between the American Geriatric Society Beers, Brazilian Consensus, and PRISCUS criteria was high or excellent. There was an independent association between polypharmacy and the use of PIMs and medications of concern by older patients with multiple myeloma. (AU)

Suitability of new drugs registered in Brazil from 2003 to 2013 for pediatric age groups.

OBJECTIVE: To analyze suitability of new drugs registered in Brazil from 2003 to 2013 for pediatric age groups. METHODS: A descriptive study of drugs with pediatric indication included in a retrospective cohort of new drugs registered in Brazil. The evaluation of drug suitability for the pediatric age group was performed using the following criteria: suitability of dosage form and capacity to deliver the recommended dose. The drugs were considered adequate for the pediatric age groups when they met both criteria. The statistical analysis included calculation of frequencies and proportions. RESULTS: Suitability due to the drug capacity to deliver the recommended dose was greater than 80% across all age groups. Regarding suitability of the dosage form, we identified that the older the age group, the greater suitability for pediatric use. Concerning the drugs presented in solid dosage form, we showed that half were classified as inadequate for one or more pediatric age groups to whom they were indicated. The adequacy of drugs to the pediatric age group was 64.3% for preschool children, 66.7% for full-term newborns, 66.7% for premature newborns, and over 70% for other age groups. CONCLUSION: Drugs for children aged under 6 years were less often adequate, considering the dosage form and capacity to provide the recommended dose. The availability and proportional suitability of medicines for pediatric use are greater for older age groups, according to age groups the drug is registered for.

Parasitological evaluation of lettuce served in school meals at a Federal State School in Rio de Janeiro, Brazil

The Brazilian "National School Lunch Program" (PNAE) must provide healthy food for students in public primary education. Thus, it is necessary to ensure both nutritional and parasitological quality, reducing health risks. Vegetables must be clean, presenting no parasites and larvae, according to Brazilian legislation. Lettuce (Lactuca sativa L.) is one of the favorite vegetables among students, and is eaten raw in salads. This paper aims to evaluate the parasitological quality of lettuce served in school lunches. 72 samples of leaf lettuce, 36 from conventional agriculture (CA) and 36 from family agriculture (FA), were analyzed. Half the samples in each group were sanitized by immersion in a sodium hypochlorite solution, with 2% active stabilized chlorine for 10 minutes (n=18/each) and half were not sanitized (n=18/each). Parasite load evaluation was performed by two methods in each subgroup: spontaneous sedimentation (SS) and sedimentation by centrifugation (SC). The parasite frequencies found were evaluated by the chi-squared test. Medically relevant parasites identified were helminths (Strongyloides stercoralis, Ascaris lumbricoides and Hookworms) as well as protozoa (Balantidium coli and Entamoeba coli). 44.6% of the FA samples presented some form of parasite by SS evaluation and 33.4% by SC evaluation; 66.7% of the CA samples presented parasites by SS evaluation, and 44.5% by SC evaluation. No significant differences were noted between the FA and CA groups in either technique. No parasites were found in any of the sanitized lettuces, regardless of the subgroup or technique applied. These results evidence the importance of adequate training and guidance for vegetable growers, food handlers as well as the general population regarding proper hygiene of lettuce leaves prior to consumption.

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 resistance protein, osteopontin and suppressor of cytokine signaling 3 genes. The combined analysis of the suppressor of cytokine signaling 3 and IL28B genotypes more effectively predicted sustained virologic response than IL28B analysis alone.

Suitability of new drugs registered in Brazil from 2003 to 2013 for pediatric age groups / Adequação às faixas etárias pediátricas de medicamentos novos registrados no Brasil de 2003 a 2013

ABSTRACT Objective To analyze suitability of new drugs registered in Brazil from 2003 to 2013 for pediatric age groups. Methods A descriptive study of drugs with pediatric indication included in a retrospective cohort of new drugs registered in Brazil. The evaluation of drug suitability for the pediatric age group was performed using the following criteria: suitability of dosage form and capacity to deliver the recommended dose. The drugs were considered adequate for the pediatric age groups when they met both criteria. The statistical analysis included calculation of frequencies and proportions. Results Suitability due to the drug capacity to deliver the recommended dose was greater than 80% across all age groups. Regarding suitability of the dosage form, we identified that the older the age group, the greater suitability for pediatric use. Concerning the drugs presented in solid dosage form, we showed that half were classified as inadequate for one or more pediatric age groups to whom they were indicated. The adequacy of drugs to the pediatric age group was 64.3% for preschool children, 66.7% for full-term newborns, 66.7% for premature newborns, and over 70% for other age groups. Conclusion Drugs for children aged under 6 years were less often adequate, considering the dosage form and capacity to provide the recommended dose. The availability and proportional suitability of medicines for pediatric use are greater for older age groups, according to age groups the drug is registered for.

RESUMO Objetivo Analisar a adequação às faixas etárias pediátricas dos medicamentos novos registrados no Brasil no período de 2003 a 2013. Métodos Estudo descritivo dos medicamentos com indicação pediátrica incluídos em uma coorte retrospectiva de medicamentos novos registrados no Brasil. A avaliação da adequação do medicamento à faixa etária pediátrica foi realizada empregando os seguintes critérios: adequação da forma farmacêutica e capacidade de fornecer a dose recomendada. Os medicamentos foram considerados adequados às faixas etárias pediátricas quando preencheram os dois critérios. A análise estatística compreendeu cálculo de frequências e proporções. Resultados A adequação devido à capacidade do medicamento fornecer a dose recomendada foi superior a 80% em todas as faixas etárias. Em relação à adequação da forma farmacêutica, identificou-se que quanto maior a faixa etária, maior a proporção de adequação para uso pediátrico. Em relação aos medicamentos que se apresentavam em formas farmacêuticas sólidas, evidenciou-se que metade foi classificada como inadequada para uma ou mais faixas etárias pediátricas para as quais estavam indicados. A adequação dos medicamentos à faixa etária pediátrica foi 64,3% para pré-escolares, 66,7% para recém-nascidos a termo, 66,7% para recém-nascidos prematuros e superior a 70% para as demais faixas etárias. Conclusão Os medicamentos destinados às crianças menores de 6 anos apresentaram menor frequência de adequação, considerando a forma farmacêutica e a capacidade de fornecer a dose recomendada. A disponibilidade e a proporção de adequação dos medicamentos para uso pediátrico aumentam com a elevação da faixa etária para a qual o medicamento é registrado.

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.

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.

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 CCR5A32 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 CCR5A32 e CCR264I. Os indivíduos infectados pelo HIV-1 apresentaram contribuição africana de 47por cento. As mutações CCR5A32 e CCR264I foram mais frequentes nos indivíduos brancos (3por cento) e negros (18por 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.(AU)

Migração, estrutura populacional, tipos de casamentos e doenças genéticas / Migration, population structure, types of marriages and genetic diseases

A migração é o fator evolutivo capaz de dispersar a diversidade genética entre populações, inserindo novas características fenotípicas e genotípicas. A dinâmica matrimonial, juntamente como a estrutura da população são fatores que podem alterar a frequência destas características. Exemplo dessas características são as doenças genéticas, onde a frequência e distribuição destas auxilia na compreensão da influência de fatores evolutivos em uma população. No município de Monte Santo, localizado no interior da Bahia, foram encontradas doenças genéticas com elevada frequência, como mucopolissacaridose do tipo VI e fenilcetonúria. Existem evidências que algumas doenças mostram associação entre a raça e o risco de sua ocorrência. Dados moleculares mostraram que na Bahia a contribuição africana é de 47,2%, entretanto, dados baseados em classificação fenotípica apontam para o aumento da contribuição europeia com o afastamento do litoral. Para inferir a origem de algumas doenças genéticas em Monte Santo foram analisados marcadores informativos de ancestralidade autossômicos (AT3-I/D, APO, PV92 e SB19.3 genotipados por PCR; GC*1F e GC*1S por PCR/RFLP; e os marcadores FYnull, CKMM e LPL por PCR em tempo real) e marcadores uniparentais do mtDNA (sequenciamento da região HVS-I) e do cromossomo Y (marcador YAP por PCR; DYS 199, 92R7 e M207 por PCR/RFLP; e M60, PN2, PN3, M34, M89, M9 por sequenciamento). Assim, através da identificação da origem desses marcadores foi possível inferir a contribuição das populações que formaram a população de Monte Santo, e a origem de algumas das alterações gênicas responsáveis pelas doenças genéticas aqui estudadas (síndrome de Treacher Collins, hipotireoidismo congênito, fenilcetonúria, mucopolissacaridose tipo VI, surdez hereditária não sindrômica e osteogênese imperfeita). Os dados do cromossomo Y e dos autossômicos apontam para maior contribuição europeia, e os resultados dos marcadores mitocondriais para elevada contribuição africana e ameríndia. A elevada contribuição europeia tanto paterna quanto autossômica sugere origem europeia para as mutações c.35delG e R252W, responsáveis por aproximadamente 24% dos casos de surdez hereditária não sindrômica e por todos os casos de fenilcetonúria, respectivamente. A mucopolissacaridose do tipo VI tem como causa a mutação p.H178L, a presença desta alteração apenas em pacientes brasileiros, que compartilham o mesmo haplótipo intragênico sugere origem autóctone. Além de marcadores moleculares também foram analisados os tipos de casamentos (endogâmicos, exogâmicos e entre imigrantes) e sua frequência no município. Foi observada elevada frequência de casamentos endogâmicos e baixa taxa de migração, sugerindo crescimento populacional interno. Além disso, a maioria da população reside em povoados, cujo tamanho varia de 113 a 582 pessoas por povoado. Nesta cidade 80% da população tem renda mensal equivalente a meio salário mínimo, o que explica baixa taxa de migração por ausência de atrativos econômicos. Avaliando os casamentos dentro das genealogias dos afetados é possível observar que a maioria 8 deles é filho de pais consanguíneos. Estes resultados mostram que o elevado grau de endogamia e endocruzamento assim como possível efeito fundador e deriva genética estão associados ao aumento da frequência e manutenção das doenças genéticas neste município.