Prevalence of clinically relevant UGT1A alleles and haplotypes in African populations

Variation of a short (TA)(n) repeat sequence (rs8175347) covering the TATA box of UGT1A1 (UDP-glucuronosyltransferase1A1) is associated with hyperbilirubinaemia (Gilbert's syndrome) and adverse drug reactions, and is used for dosage advice for irinotecan. Several reports indicate that the low-activity (risk) alleles ((TA)(7) and (TA)(8) )) are very frequent in Africans but the patterns of association with other variants in the UGT1A gene complex that may modulate these responses are not well known. rs8175347 and two other clinically relevant UGT1A variants (rs11692021 and rs10929302) were assayed in 2616 people from Europe and Africa. Low-activity (TA)(n) alleles frequencies were highest in equatorial Africa, (TA)(7,) being the most common in Cameroon, Ghana, southern Sudan, and in Ethiopian Anuak. Haplotypic diversity was also greatest in equatorial Africa, but in Ethiopia was very variable across ethnic groups. Resequencing of the promoter of a sample subset revealed no novel variations, but rs34547608 and rs887829 were typed and shown to be tightly associated with (TA)(n) . Our results illustrate the need for investigation of the effect of UGT1A variants other than (TA)(n) on the risk of irinotecan toxicity, as well as hyperbilirubinaemia due to hemolytic anaemia or human immunodeficiency virus protease inhibitors, so that appropriate pharmacogenetic advice can be given.     

Intussusception in adolescents and adults: a report on cases from Addis Ababa, Ethiopia, during a three-year period

BACKGROUND: Though there are few studies, mainly on children, very little is known about its occurrence in Ethiopian adults. OBJECTIVE: To assess the clinical presentations, clinical findings, operative findings (including types and identification of specific causes), modes of treatment, and postoperative outcome in adult patients operated for intussusception. METHODS: A retrospective review of adolescent and adult patients' record with intra operative diagnosis of intussusception over a period of three years in three teaching Hospitals in Addis Ababa, Ethiopia, i.e. Tikur Anbassa (TAH), Princess Zewditu Memorial (ZMH) and St. Paul's Hospitals (SPH). RESULTS: A total of 25 patients were analyzed. Two peak ages of occurrence were identified i.e. the 2nd decade, which represented mainly idiopathic intussusception, and the 4th decade, which was mainly of secondary type. The median duration of illness was 144 hours with a range of 6-720 hours. The Ileo-colic type was identified in 14 (56%) of the cases. Fifteen (60%) cases were primary (Idiopathic). Benign conditions represented the majority (67%) of the identified lead points. Intra operative reduction was successful in only 6 (24%) of the cases, all of which were idiopathic. Four of our patients died giving an overall mortality rate of 16%. All of the deaths were from the idiopathic variety. Irreversible septic shock with multi organ failure was the cause of death. CONCLUSION: Intussusception is not a rare disease in Ethiopian adults, the primary idiopathic variant occurring with a higher frequency. Identified lead points are usually benign, especially if they are situated in the small intestine. En-block resection of the involved intestinal segment should be the rule if there is an obvious ischemic change and limited resection is recommended if a lead point is identified.