Thalassemia minor, the Gilbert mutation, and the risk of gallstones.
OBJECTIVE
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.


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].


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.
Borgna-Pignatti
Caterina
C
Department of Clinical and Experimental Medicine-Pediatrics, University of Ferrara, via Savonarola 9, 44100 Ferrara, Italy. borgna@unife.it
Rigon
Francesca
F
Merlo
Luciano
L
Chakrok
Roksana
R
Micciolo
Rocco
R
Perseu
Luciana
L
Galanello
Renzo
R
D000483:Alleles; D002769:Cholelithiasis / Q000453:epidemiology / Q000235:genetics; D005260:Female; D042882:Gallstones / Q000453:epidemiology* / Q000235:genetics; D005838:Genotype; D005878:Gilbert Disease / Q000235:genetics*; D014453:Glucuronosyltransferase / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D009154:Mutation / Q000235:genetics*; D015995:Prevalence; D012306:Risk; D017086:beta-Thalassemia / Q000097:blood / Q000201:enzymology / Q000453:epidemiology* / Q000235:genetics; D000099148:UGT1A1 Enzyme
D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme