Evaluation of the effects of VKORC1 polymorphisms and haplotypes, CYP2C9 genotypes, and clinical factors on warfarin response in Sudanese patients.

OBJECTIVE: African populations, including the Sudanese, are underrepresented in warfarin pharmacogenetic studies. We designed a study to determine the associations between the polymorphisms and haplotype structures of CYP2C9 and VKORC1 and warfarin dose response in Sudanese patients, one of the most genetically diverse populations in Africa. MATERIAL AND METHODS: The effect of the CYP2C9 polymorphisms (*2, *3, *5, *6, *8, *9, and *11), 20 VKORC1 tag SNPs and haplotypes, and clinical covariates were comprehensively assessed in 203 Sudanese warfarin-treated patients. RESULTS: Patients with the CYP2C9*2,*5,*6, or *11 variant required a daily warfarin dose that was 21% lower than those with CYP2C9*1/*1 (4.7 vs 5.8 mg/day, P < 0.001). SNPs around the VKORC1 and POL3S genes were divided into two haplotype blocks in Sudanese populations. According to multiple linear regression results, rs8050984, rs7294, and rs7199949 in the VKORC1 and POL3S genes (P <0.001, <0.001, <0.001, respectively), CYP2C9 genotype (*2, *5, *6, *11; P < 0.001), body weight (P = 0.04), target INR (P = 0.007), and concurrent medications (P = 0.029) could explain about 36.7% of the total warfarin dose variation. CONCLUSION: Our data revealed that VKORC1 and CYP2C9 polymorphisms are important factors that influence warfarin dose response in Sudanese patients. Our data suggest that combinations of the SNPs may improve predictions of warfarin dose requirements.

Tuberculoma of the brain: a series of 16 cases treated with anti-tuberculosis drugs.

OBJECTIVES: To describe the clinical presentation, radiological findings and outcome of treatment with antituberculosis drugs in 16 cases of intracranial tuberculoma. DESIGN: Consecutive cases admitted with tuberculoma to the National Center for Neurological Diseases in Khartoum, Sudan, were included in the study. The diagnosis was based on clinical and neuro-imaging features and response to anti-tuberculosis treatment. Histopathology of material from the brain or other extracranial tissues was available in seven cases. RESULTS AND CONCLUSIONS: The commonest presenting features were headache (100%), generalized convulsions (68.7%) and hemiparesis (56.2%). Computerised axial tomography/magnetic resonance imaging (CT/MRI) showed single or multiple lesions that showed intense contrast enhancement and perilesional edema. The lesions completely cleared on anti-tuberculosis treatment in the majority of survivors (13/15). Partial clearance of lesion was associated with late presentation, multiple large lesions and advanced miliary disease. We advocate early empirical trial of anti-tuberculosis drugs for intracranial tuberculoma even after a presumptive diagnosis, particularly in areas where the infection is endemic.