尿苷二磷酸葡萄糖醛酸基转移酶1A1启动子和编码区突变与β地中海贫血/Hb E合并胆结石的关联。

Association between promoter and coding region mutations of UDP-glucuronosyltransferase 1A1 and beta-thalassemia/Hb E with cholelithiasis.

作者信息

Tankanitlert Jeeranut, Morales Noppawan P, Fucharoen Pranee, Fucharoen Suthat, Chantharaksri Udom

机构信息

Department of Pharmacology, Phramongkutklao College of Medicine, Bangkok, Thailand.

出版信息

Eur J Haematol. 2008 Apr;80(4):351-5. doi: 10.1111/j.1600-0609.2007.01010.x. Epub 2007 Dec 10.

DOI:10.1111/j.1600-0609.2007.01010.x

PMID:18081723

Abstract

BACKGROUND AND OBJECTIVES

Cholelithiasis has been observed with high incidence in beta-thalassemia/hemoglobin E (beta-thal/Hb E). Recent studies have shown that a variant TATA-box in the promoter region of the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene is associated with the development of cholelithiasis. The coding region mutation (G71R) of the UGT1A1 gene was higher in Asians than those in Caucasians. The relationship between the variant UGT1A1 promoter and coding region gene and cholelithiasis in beta-thal/Hb E subjects were investigated.

METHODS

One hundred and seventeen beta-thal/Hb E subjects entered this study. The TATA-box and G71R mutations were analyzed by fragment size analysis and restriction fragment length polymorphism methods, respectively.

RESULTS

The incidence of cholelithiasis was higher in heterozygous (68.3%) and homozygous (100%) subjects compared with normal UGT1A1 haplotype (61.4%). Total bilirubin level (6.0 +/- 2.03 mg/dL) in the homozygous group was significantly higher than that of wild type (3.31 +/- 1.83 ng/dL). Prevalence of cholelithiasis increased with age (OR = 1.1, 95% CI = 1.03-1.12, P < 0.001). Female gender (OR = 3.7, 95% CI = 1.3-10.6, P < 0.01) and elevated liver enzyme (OR = 1.02, 95%CI = 1.0-1.04, P < 0.02) were two other risk factors for cholelithiasis in beta-thal/Hb E.

CONCLUSION

This study shows that the combined TATA-box variants and G71R mutations of the UGT1A1 is associated with cholelithiasis in beta-thal/Hb E.

摘要

背景与目的

在β地中海贫血/血红蛋白E（β-地贫/Hb E）患者中，胆结石的发病率较高。近期研究表明，尿苷二磷酸葡萄糖醛酸基转移酶1A1（UGT1A1）基因启动子区域的一个TATA框变异与胆结石的发生有关。UGT1A1基因的编码区突变（G71R）在亚洲人中的发生率高于白种人。本研究旨在探讨β-地贫/Hb E患者中UGT1A1启动子变异和编码区基因与胆结石之间的关系。

方法

117例β-地贫/Hb E患者纳入本研究。分别采用片段大小分析和限制性片段长度多态性方法分析TATA框和G71R突变。

结果

与正常UGT1A1单倍型（61.4%）相比，杂合子（68.3%）和纯合子（100%）患者的胆结石发病率更高。纯合子组的总胆红素水平（6.0±2.03mg/dL）显著高于野生型（3.31±1.83ng/dL）。胆结石的患病率随年龄增长而增加（OR = 1.1，95%CI = 1.03 - 1.12，P < 0.001）。女性（OR = 3.7，95%CI = 1.3 - 10.6，P < 0.01）和肝酶升高（OR = 1.02，95%CI = 1.0 - 1.04，P < 0.02）是β-地贫/Hb E患者胆结石的另外两个危险因素。