An analysis of UGT1A1 genotype-phenotype correlation in Chinese patients with Gilbert and Crigler-Najjar II syndrome

Abstract Background: The spectrum of UDP-glucuronosyltransferase (UGT1A1) variants, which are associated with Gilbert syndrome (GS) and Crigler-Najjar syndrome (CNS-II), has been reported in Chinese and western countries. However, the genotype-phenotype correlation of the individual UGT1A1 variants in GS and CNS-II remains to be clarified. Methods: To explore the UGT1A1 variant pattern and genotype-phenotype correlations, we enrolled 310 Chinese patients, including 232 patients with GS and 78 with CNS-II. Peripheral blood samples were collected from screening variants in the gene UGT1A1 by a polymerase chain reaction and Sanger sequencing. The correlation between different UGT1A1 variants and clinical phenotypes was analyzed. Results: Total cholesterol and serum high-density lipoprotein levels were higher in patients with GS than those with CNS-II. A total of 21 UGT1A1 variants were identified, including nine novel variants, four of which are in-silico predicted to be probably damaging. The allele frequency showed that the most common variants were A(TA)7TAA, p.G71R, p.Y486D, p.P364L, and p.P229Q, which are different from western countries. The mean value of serum total bilirubin in patients with the p.Y486D variant in both heterozygote and homozygote was significantly high compared with other high-frequency variants. Additionally, serum triglyceride and low-density lipoprotein in patients with a heterozygous p.P229Q variant were significantly elevated compared with other high-frequency variants. Conclusions: The spectrum of UGT1A1 variants in Chinese patients appears distinct from western countries. Total bilirubin and plasma lipid are different among the individual UGT1A1 variants.