Analysis of UGT1A1 genotype-phenotype correlation in Chinese patients with gilbert and crigler-Najjar II syndrome

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. 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 for 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. A total of 21 UGT1A1 variants were identified, including nine novel variants, and constituted 42 UGT1A1 genotypes in the GS and CNS-II patients. The most common UGT1A1 variants were A (TA)₇TAA, p.G71R, p.Y486D, p.P364L, and p.P229Q, which were different from western countries. The p.Y486D variant had higher minor allele frequency in CNS-II than in GS whereas the A (TA)₇TAA variant had higher minor allele frequency in GS than in CNS-II. The serum total bilirubin and triglyceride had significant differences among 14 recurrent genotypes of UGT1A1, in which the serum total bilirubin in patients with compound p.Y486D (homozygous)/p.G71R variant was significantly higher compared with homozygous A (TA)₇TAA, homozygous p.G71R, compound heterozygous A (TA)₇TAA/p.G71R and A (TA)₇TAA/p.P364L, and combined heterozygous A (TA)₇TAA/p.G71R/p.P229Q, while the serum triglyceride in patients with combined A (TA)₇TAA (homozygous)/p.P229Q variant was significantly higher compared with compound heterozygous A (TA)₇TAA/p.G71R, single heterozygous A (TA)₇TAA, single heterozygous p.G71R, and homozygous A (TA)₇TAA. The spectrum of UGT1A1 genotypes in Chinese patients was distinct from western countries. There were differential levels of serum total bilirubin and triglyceride in patients with recurrent genotypes of UGT1A1.