Effects of variant UDP-glucuronosyltransferase 1A1 gene, glucose-6-phosphate dehydrogenase deficiency and thalassemia on cholelithiasis.
OBJECTIVE
To test the hypothesis that the variant UDP-glucuronosyltransferase 1A1 (UGT1A1) gene, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and thalassemia influence bilirubin metabolism and play a role in the development of cholelithiasis.


METHODS
A total of 372 Taiwan Chinese with cholelithiasis who had undergone cholecystectomy and 293 healthy individuals were divided into case and control groups, respectively. PCR and restriction fragment length polymorphism were used to analyze the promoter area and nucleotides 211, 686, 1,091, and 1,456 of the UGT1A1 gene for all subjects and the gene variants for thalassemia and G6PD deficiency.


RESULTS
Variation frequencies for the cholelithiasis patients were 16.1%, 25.8%, 5.4%, and 4.3% for A(TA)(6) TAA/A(TA)(7)TAA (6/7), heterozygosity within the coding region, compound heterozygosity, and homozygosity of the UGT1A1 gene, respectively. Comparing the case and control groups, a statistically significant difference in frequency was demonstrated for the homozygous variation of the UGT1A1 gene (P = 0.012, chi(2) test), but not for the other variations. Further, no difference was demonstrated in a between-group comparison of the incidence of G6PD deficiency and thalassemia (2.7% vs 2.4% and 5.1% vs 5.1%, respectively). The bilirubin levels for the cholelithiasis patients with the homozygous variant-UGT1A1 gene were significantly different from the control analog (18.0+/-6.5 and 12.7+/-2.9 micromol/L, respectively; P<0.001, Student's t test).


CONCLUSIONS
Our results show that the homozygous variation in the UGT1A1 gene is a risk factor for the development of cholelithiasis in Taiwan Chinese.
Huang
Yang-Yang
YY
Department of Laboratory Medicine, Cathay General Hospital, Taipei, Taiwan, China.
Huang
Ching-Shui
CS
Yang
Sien-Sing
SS
Lin
Min-Shung
MS
Huang
May-Jen
MJ
Huang
Ching-Shan
CS
D000328:Adult; D001663:Bilirubin / Q000378:metabolism; D016022:Case-Control Studies; D002681:China / Q000208:ethnology; D002769:Cholelithiasis / Q000150:complications* / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000150:complications* / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D013624:Taiwan; D013789:Thalassemia / Q000150:complications* / Q000378:metabolism*; D000099148:UGT1A1 Enzyme
D001663:Bilirubin; D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme