Genetic interactions in Taiwanese adults with unconjugated hyperbilirubinemia

• Main Author: 黃美真
• Other Authors: 華國媛
• Format: Others
• Language: zh-TW
• Published: 2003
• Online Access: http://ndltd.ncl.edu.tw/handle/07200771903453982550

碩士 === 臺北醫學大學 === 生物醫學技術研究所 === 91 === Unconjugated hyperbilirubinemia is associated with (1) increased erythrocyte hemolysis, (2) decreased hepatic uptake of unconjugated bilirubin and (3) decreased conjugation of bilirubin. The aim of this study is to investigate whether the genetic interactions among the genes involved in the metabolism of bilirubin influence bilirubin levels in Taiwanese healthy adults with unconjugated hyperbilirubinemia. One hundred and three Taiwanese healthy adults with unconjugated hyperbilirubinemia and 100 random controls were recruited. All subjects were analyzed for G6PD, OATP2, UGT1A1 genotypes by PCR-RFLP (polymerase chain reaction — restriction fragment length polymorphism) method, and were compared using the chi-square test, t-test, ANOVA and logistic regression. The results showed that the allelic frequency of OATP2 nt 388A in the unconjugated hyperbilirubinemia subjects was higher than the frequency in the control subjects (29.6% vs. 20.5%, p=0.035), but there was no significant differences in nt 521 distributions between the two groups. The incidence of G6PD deficiency was 18.4% and the overall variation rate of UGT1A1 gene was 92.2% in unconjugated hyperbilirubinemia group. Subjects with the coinheritance of G6PD deficiency and UGT1A1 variations were higher risk to develop unconjugated hyperbilirubinemia than subjects with G6PD deficiency or UGT1A1 variations along, and the OR (95% CI) were 168.8 (17.5-1630), 22.5 (3.1-163.2) and 17.3 (5.9-51.0), respectively. OATP2 nt 388 AA or AG could increase the risk ratio of unconjugated hyperbilirubinemia in G6PD normal coexisted with UGT1A1 variations. All the suspicious risk factors of unconjugated hyperbilirubinemia in Taiwanese adults, such as homozygous UGT1A1 variation, compound heterozygous UGT1A1 variation, G6PD deficiency, Hb, heterozygous UGT1A1 variation and OATP2-388 AG or AA were compared using the logistic regression analyses, the OR (95%CI) were 292.6 (30-2854), 58.2 (15.5-218.8), 32.0 (6.4-159.2), 5.7 (2.2-14.7), 3.8 (1.2-12.0) and 2.8 (1.2-6.6), respectively. The results indicated that homozygous UGT1A1 variation including homozygous A(TA)7TAA (77.4%) and homozygous 211A (22.6%), was the most important risk factor for unconjugated hyperbilirubinemia. In conclusion, the results of my study suggest that genetic interactions among the genes associated with bilirubin metabolism are involved in the development of unconjugated hyperbilirubinemia in Taiwanese healthy adults.