Background and objectives: Gallstones are a frequent complication of hemolytic anemias. The association with the mutation of the A(TA)nTAA motif of the promoter of the bilirubin UDP-glucuronosyltransferase gene has also been reported to increase the risk of gallstones. We studied the prevalence of cholelithiasis in thalassemia minor and the role of the Gilbert mutation.
Design and methods: A group of 143 women obligate carriers of beta-thalassemia, and a control group of 170 hematologically normal women were compared. In both groups serum bilirubin, total cholesterol, and alanine-aminotransferase were measured and analysis of the mutation of the UGT-1A gene was performed. On the same occasion the women underwent ultrasonography.
Results: Total and unconjugated bilirubin were significantly higher in beta-thalassemia heterozygotes. Carriers of thalassemia had a higher prevalence of gallstones (20.3% vs 10.6% OR=2.15). Among the control group, the prevalence of gallstones did not differ significantly in relation to UGT1-A1 genotype, while in women carriers of beta-thalassemia it increased in an allele dose-dependent fashion. As compared to the controls, the odds ratios for the development of gallstones in thalassemic women were 1.68 (95% C.I.: 0.70-4.03) for those who had the normal UGT1-A1 genotype [(TA)6/(TA)6], 2.31 (95% C.I.: 1.06-5.02) for heterozygote carriers of the mutated genotype [(TA)7/(TA)6] and 3.88 (95% C.I.: 1.31-11.55) for those homozygous for the mutated genotype [(TA)7/(TA)7].
Interpretation and conclusions: Thalassemia minor represents a risk factor for cholelithiasis and the Gilbert mutation further increases this risk. This is an additional example of how two genotypes can interact and modify a phenotype.