RESUMO
Fetal hemoglobin (HbF) levels are higher in the Arab-Indian (AI) ß-globin gene haplotype of sickle cell anemia compared with African-origin haplotypes. To study genetic elements that effect HbF expression in the AI haplotype we completed whole genome sequencing in 14 Saudi AI haplotype sickle hemoglobin homozygotes-seven selected for low HbF (8.2% ± 1.3%) and seven selected for high HbF (23.5% ± 2.6%). An intronic single nucleotide polymorphism (SNP) in ANTXR1, an anthrax toxin receptor (chromosome 2p13), was associated with HbF. These results were replicated in two independent Saudi AI haplotype cohorts of 120 and 139 patients, but not in 76 Saudi Benin haplotype, 894 African origin haplotype and 44 AI haplotype patients of Indian origin, suggesting that this association is effective only in the Saudi AI haplotype background. ANTXR1 variants explained 10% of the HbF variability compared with 8% for BCL11A. These two genes had independent, additive effects on HbF and together explained about 15% of HbF variability in Saudi AI sickle cell anemia patients. ANTXR1 was expressed at mRNA and protein levels in erythroid progenitors derived from induced pluripotent stem cells (iPSCs) and CD34+ cells. As CD34+ cells matured and their HbF decreased ANTXR1 expression increased; as iPSCs differentiated and their HbF increased, ANTXR1 expression decreased. Along with elements in cis to the HbF genes, ANTXR1 contributes to the variation in HbF in Saudi AI haplotype sickle cell anemia and is the first gene in trans to HBB that is associated with HbF only in carriers of the Saudi AI haplotype. Am. J. Hematol. 91:1118-1122, 2016. © 2016 Wiley Periodicals, Inc.
Assuntos
Anemia Falciforme/genética , Hemoglobina Fetal/genética , Haplótipos , Adolescente , Adulto , Árabes/genética , Proteínas de Transporte/genética , Criança , Pré-Escolar , Feminino , Expressão Gênica , Humanos , Masculino , Proteínas dos Microfilamentos , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Polimorfismo de Nucleotídeo Único , Receptores de Superfície Celular/genética , Proteínas Repressoras , População Branca/genética , Adulto Jovem , Globinas beta/genéticaAssuntos
Anemia Falciforme/genética , Proteínas de Ligação a DNA/genética , Família Multigênica , Fatores de Transcrição/genética , Globinas beta/genética , Motivos de Aminoácidos , Anemia Falciforme/metabolismo , Proteínas de Ligação a DNA/metabolismo , Feminino , Humanos , Masculino , Fatores de Transcrição/metabolismo , Globinas beta/metabolismoRESUMO
BACKGROUND: Fetal hemoglobin (HbF) levels in sickle cell anemia patients vary. We genotyped polymorphisms in the erythroid-specific enhancer of BCL11A to see if they might account for the very high HbF associated with the Arab-Indian (AI) haplotype and Benin haplotype of sickle cell anemia. METHODS AND RESULTS: Six BCL112A enhancer SNPs and their haplotypes were studied in Saudi Arabs from the Eastern Province and Indian patients with AI haplotype (HbF ~20%), African Americans (HbF ~7%), and Saudi Arabs from the Southwestern Province (HbF ~12%). Four SNPs (rs1427407, rs6706648, rs6738440, and rs7606173) and their haplotypes were consistently associated with HbF levels. The distributions of haplotypes differ in the 3 cohorts but not their genetic effects: the haplotype TCAG was associated with the lowest HbF level and the haplotype GTAC was associated with the highest HbF level and differences in HbF levels between carriers of these haplotypes in all cohorts were approximately 6%. CONCLUSIONS: Common HbF BCL11A enhancer haplotypes in patients with African origin and AI sickle cell anemia have similar effects on HbF but they do not explain their differences in HbF.
Assuntos
Anemia Falciforme/genética , Proteínas de Transporte/genética , Hemoglobina Fetal/genética , Proteínas Nucleares/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Negro ou Afro-Americano/genética , Árabes/genética , Povo Asiático/genética , Criança , Feminino , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Repressoras , Adulto JovemRESUMO
We aimed to test the knowledge, attitude and practice (KAP) of physicians towards erectile dysfunction in the Eastern province of Saudi Arabia. At a scientific meeting about erectile dysfunction, 159 physicians from both government and private sectors answered a 34-item questionnaire in private. The mean total KAP score for the group was below the expected standard of 60%. Male physicians scored significantly higher than females. Urologists scored the highest, followed by andrologists. Surprisingly, physicians with higher qualifications scored lower than those with intermediate qualifications and even less than general practitioners. Those who had practised for > or = 10 years scored better than those with < 10 years practice. The role of cardiologists in the diagnosis and management of erectile dysfunction is discussed.
Assuntos
Atitude do Pessoal de Saúde , Disfunção Erétil , Conhecimentos, Atitudes e Prática em Saúde , Médicos , Padrões de Prática Médica/organização & administração , Cardiologia/educação , Cardiologia/organização & administração , Competência Clínica/normas , Estudos Transversais , Currículo , Educação Médica , Educação de Pós-Graduação em Medicina , Educação de Graduação em Medicina , Avaliação Educacional , Disfunção Erétil/diagnóstico , Disfunção Erétil/epidemiologia , Disfunção Erétil/etiologia , Disfunção Erétil/terapia , Feminino , Necessidades e Demandas de Serviços de Saúde , Humanos , Masculino , Medicina/organização & administração , Papel do Médico , Médicos/organização & administração , Médicos/psicologia , Saúde Pública , Arábia Saudita/epidemiologia , Especialização , Inquéritos e QuestionáriosRESUMO
We aimed to test the knowledge, attitude and practice [KAP] of physicians towards erectile dysfunction in the Eastern province of Saudi Arabia. At a scientific meeting about erectile dysfunction, 159 physicians from both government and private sectors answered a 34-item questionnaire in private. The mean total KAP score for the group was below the expected st and ard of 60%. Male physicians scored significantly higher than females. Urologists scored the highest, followed by and rologists. Surprisingly, physicians with higher qualifications scored lower than those with intermediate qualifications and even less than general practitioners. Those who had practised for >/= 10 years scored better than those with < 10 years practice. The role of cardiologists in the diagnosis and management of erectile dysfunction is discussed
Assuntos
Cardiologia , Competência Clínica , Estudos Transversais , Currículo , Educação de Pós-Graduação em Medicina , Necessidades e Demandas de Serviços de Saúde , Disfunção Erétil , Papel do Médico , Saúde Pública , Inquéritos e Questionários , Atitude do Pessoal de SaúdeRESUMO
OBJECTIVE: To evaluate the prevalence and pattern of antituberculous drug resistance and patients with pulmonary tuberculosis in the Eastern Province and its impact on the tuberculosis control program. METHODS: Patients with pulmonary tuberculosis, proven by culture, admitted to Dammam Chest Hospital from November 1993 through May 1996 were reviewed. Patients who had at least one documented isolate of mycobacterium tuberculosis resistant to at least one standard anti-tuberculosis drug were identified. Medical records were reviewed and information was retrieved regarding age, sex, nationality, history of previous tuberculosis, human immune deficiency status, and results of direct smear and chest radiograph abnormalities. RESULTS: A total of 411 cases of culture positive pulmonary tuberculosis with drug susceptibility testing, were identified during the period mentioned, of these 123 (30%) were Saudi nationals and 228 (70%) were non-Saudis. Drug resistance to at least one drug was observed in 43 (10.5%) patients, resistance to isoniazid alone was observed in 25 (6%) patients, whereas resistance to rifampicin was noted in only one (0.2%) patient, and to streptomycin in 3 (1%) patients, multidrug resistance was observed in 11 (3%) patients. CONCLUSION: The study has shown that the overall drug resistance rate of 10.5% in the Eastern Province of Saudi Arabia is the lowest reported in the Kingdom, compared with Riyadh (13%), Taif (23%) and Gizan (44%). However, it appears to be similar to that reported in neighboring countries. In light of the study findings, and as per the recommendation of the World Health Organization, we suggest that a 4-drug regimen, as an initial treatment for pulmonary tuberculosis should be maintained, as resistance to isoniazid is still higher than the cut off value of 4%, and susceptibility testing for first line antituberculosis drugs should be carried out whenever possible. We also recommend applying stricter medical criteria for tuberculosis screening in newcomers, and for Saudi nationals, application of directly observed therapy should be a priority.
