| Summary: | Objective To clarify the linkage of pathogenic mutations in UDP-glucuronyl transferase 1A1 (UGT1A1) gene with Gilbert syndrome (GS) and explore the genetic mechanism of GS. Methods The genomic DNA was extracted from the peripheral blood samples of 46 unrelated GS patients and 80 healthy control subjects. The enhancer PBREM, the promoter TATA box, PE, DE and the coding regions of UGT1A1 gene were amplified with PCR, and the amplified DNA fragments were sequenced and analyzed. Results Six single nucleotide polymorphisms (SNPs) were identified in UGT1A1 gene of GS patients, namely c.-3279T>G, c.-1352C>A, c.-40_-39insTA, c.211G>A, c.686C>A, and c.1456T>G. The D' and r2 were both 1 for c.-40_-39insTA and c.-3279T>G, demonstrating a complete linkage disequilibrium. Haplotype construction showed that c.-40_-39insTA was linked to c.-3279T>G, and c.211G>A was linked to c.-1352C>A; the frequency of the diplotypes generated by these haplotypes reached 0.717 in GS, as comparted to 0.005 in the control subjects (P < 0.000). Conclusion The occurrence of GS is associated with the variations of c.-40_ -39insTA and c.211G >A from different homologous chromosomes, and c.-3279T>G and c.-1352C>A both have a dose effect in their respective linkage.
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