Genetic Polymorphism of UGT1A1 Gene in Chinese

Autor: Liu, Chin Hung, 劉晉宏
Rok vydání: 1999
Druh dokumentu: 學位論文 ; thesis
Popis: 87
The UGT1A1 is a detoxifying enzyme that catalyzes the formation of glucuronic acid conjugates of several endogenous and exogenous compounds such as bilirubin, steroid hormones and many therapeutic drugs. Differences in the activity of UGT1A1 would possibly cause some toxic or carcinogenic effects. Genetic disorders in the UGT1A1 gene are responsible for both Gilbert''s and Crigler-Najjar syndromes. Gilbert''s syndrome, is a benign form of unconjugated hyperbilirubinemia by mild elevation of serum total the most prevalent ( about 3-10% in Caucasian population studies ). Comparison, the Crigler-Najjar syndrome is more rare and severe genetic defect, and is at risk for lethal neurotoxicity due to neonatal kernicterus. In the studies, we determined the promoter and five exons regains of the UGT1A1 gene, from 120 unrelated healthy Chinese by PCR-SSCP, RFLP, PCR-mismatch and automatch-sequencing methods. We have found high genetic polymorphism frequency of UGT1A1 gene in Chinese population (45% of population). In Gilbert''s syndrome related mutation sites such as UGT1A1*6 (G71R), UGT1A1*27 (P229Q), UGT1A1*28 [(TA)7TAA] and UGT1A1*29 (R367G). In the UGT1A1*6 examined, we found 120 individuals included 84 normals, and 33 heterozygous and 3 mutation homozygous. In the UGT1A1*28 examined, found 120 individuals included 101 normals, and 19 heterozygous and no homozygous mutation. Moreover, in the UGT1A1*27 and UGT1A1*29 alleles examined, no mutation were found in 120 Chinese. We also found two novel polymorphism including one missense 1091CaT (P364L) and one silent 189CaT (D63). Our results support high molecular heterogeneity of UGT1A1 gene in Chinese population and provide new insight for the diagnosis and genetic counseling of two diseases, drug metabolism and carcinogens.
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