Linkage analysis of pathogenic UGT1A1 mutations in Gilbert syndrome: a case-control study of 46 cases

Lufeng LI; Guohong DENG; Qing MAO

doi:10.16016/j.1000-5404.201908110

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Linkage analysis of pathogenic UGT1A1 mutations in Gilbert syndrome: a case-control study of 46 cases

Clinical Medicine | 更新时间：2026-01-09

- Linkage analysis of pathogenic UGT1A1 mutations in Gilbert syndrome: a case-control study of 46 cases
- Journal of Third Military Medical University Vol. 42, Issue 2, Pages: 168-175(2020)
- 作者机构：
  
  400038 重庆陆军军医大学(第三军医大学)第一附属医院感染科
- 作者简介：
- 基金信息：
  
  SWH2016ZDCX3002(SWH2016ZDCX3002)
- DOI：10.16016/j.1000-5404.201908110
  CLC： R363.21; R394.3; R596.1
- Received：15 August 2019，
  
  Revised：2019-09-22，
  
  Published：30 January 2020
- 稿件说明：
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Lufeng LI, Guohong DENG, Qing MAO. Linkage analysis of pathogenic UGT1A1 mutations in Gilbert syndrome: a case-control study of 46 cases[J]. Journal of Third Military Medical University, 2020, 42(2): 168-175.
DOI：

Lufeng LI, Guohong DENG, Qing MAO. Linkage analysis of pathogenic UGT1A1 mutations in Gilbert syndrome: a case-control study of 46 cases[J]. Journal of Third Military Medical University, 2020, 42(2): 168-175. DOI： 10.16016/j.1000-5404.201908110.

摘要

目的

明确Gilbert综合征患者(Gilbert syndrome，GS)UDP-葡萄糖醛酸基转移酶1A1基因(UDP-glucuronyl transferase 1A1 gene，UGT1A1)致病变异的连锁关系，进一步明确GS的遗传机制。

方法

对46例GS患者与80名健康对照者UGT1A1基因的增强子PBREM、启动子TATA盒、PE、DE及外显子进行直接测序，把所测得的SNP进行连锁不平衡分析、并构建单体型和单体基因型进行分析。

结果

共测到c.-3279T

G、c.-1352C

A、c.-40_-39insTA、c.211G

A、c.686C

A、c.1456T

G等6个SNP位点，对该6个SNP位点进行连锁不平衡分析表明c.-3279T

G和c.-1352C

A的D’值和r

均等于1，呈完全的连锁不平衡；进一步构建单体型表明c.-40_-39insTA和c.-3279T

G呈连锁关系、c.211G

A和c.-1352C

A呈连锁关系，他们所构成的单体基因型在病例组中的频率高达0.717，而在对照组中的频率仅为0.005，两者具有显著的统计学差异，

0.000。

结论

Gilbert综合征的发生与来源于不同同源染色体的c.-40_-39insTA和c.211G>A的两两变异相关，而c.-3279T>G和c.-1352C>A与它们的各自连锁发挥了剂量效应作用。

Abstract

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

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

c.-1352C

c.-40_-39insTA

c.211G

c.686C

and c.1456T

G. The D' and r

were both 1 for c.-40_-39insTA and c.-3279T

demonstrating a complete linkage disequilibrium. Haplotype construction showed that c.-40_-39insTA was linked to c.-3279T

and c.211G

A was linked to c.-1352C

A; the frequ

ency of the diplotypes generated by these haplotypes reached 0.717 in GS

as comparted to 0.005 in the control subjects (

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.

关键词

Keywords

references

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