The linear effects of α‐thalassaemia, the UGT1A1 and HMOX1 polymorphisms on cholelithiasis in sickle cell disease

• DOI: 10.1111/j.1365-2141.2007.06643.x
• Publication Date: 2007-06-23T02:28:14Z
• Authors: Nisha Vasavda; Stephan Menzel; Sheila Kondaveeti; Emma Maytham; Moji Awogbade; Sybil Bannister; Juliette Cunningham; Andrew Eichholz; Yvonne Daniel; Iheanyi Okpala; Tony Fulford; Swee Lay Thein
• Keywords: HMOX1; Glucuronosyltransferase; Unconjugated hyperbilirubinemia

Summary Serum bilirubin levels and predisposition to gallstones in sickle cell disease (SCD) are influenced by genetic variation the hepatic uridine diphosphate (UDP)‐glucuronosyltransferase ( UGT1A1 ) gene, but association is not consistent. This study investigated whether gene encoding haem oxygenase HMOX1 ), a rate‐limiting enzyme upstream of UGT1A catabolic pathway, α ‐thalassaemia could explain some inconsistent effects. The [TA] n [GT] promoter polymorphisms globin genotypes were determined 263 SCD patients (199 HbSS, 5 HbS/ β 0 , 59 HbSC). Detection was based on ultrasound liver/biliary tree. Regression analysis showed that serum incidence strongly associated with number repeats all subjects P < 0·0001 0·01, respectively). While genotype had no effect, co‐inheritance reduced independently repeats. Each additional repeat an increase mean 21% cholelithiasis risk 87% SCD.