Genotype of UGT1A1 and phenotype correlation between Crigler-Najjar syndrome type II and Gilbert syndrome
Genotype of UGT1A1 and phenotype correlation between Crigler-Najjar syndrome type II and Gilbert syndrome
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DOI：
10.1111/jgh.13071
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发表时间：
2016-02-01
影响因子：
4.1
通讯作者：
Takeuchi, Yoshihiro
中科院分区：
文献类型：
--
作者：
Maruo, Yoshihiro;Nakahara, Sayuri;Takeuchi, Yoshihiro
背景和目的：遗传性非结合型高胆红素血症、Crigler-Najjar综合征I型、Crigler-Najjar综合征II型（CN-2）和吉尔伯特综合征（GS）均由胆红素尿苷5 '-二磷酸（UDP）-葡萄糖醛酸转移酶基因（UGT 1A 1）突变引起。通常，区分CN-2和GS是困难的，因为这两种综合征的界限不清楚。我们分析了163例日本CN-2或GS患者的基因型和表型。方法：分析了日本非结合型高胆红素血症患者（99例男性和64例女性）。他们的血清胆红素浓度从1.2到22.2mg/dL（20到379 M）不等。通过PCR扩增直接测序进行UGT 1A 1的遗传分析。结果：大多数患者存在UGT 1A 1双等位基因突变。此外，他们中的许多人（78.5%）有多个突变。典型的CN-2突变是一个纯合的双错义突变。[G71R：Y486D]。在典型GS组中，检测到4种流行基因型：纯合子UGT 1A 1 *28、UGT 1A 1 *6/UGT 1A 1 *28、纯合子UGT 1A 1 *6和UGT 1A 1 *27/UGT 1A 1 *28。在中间组中，三种基因型，p。[G71R：Y 486 D]/UGT 1A 1 *7，第。[G71R：Y 486 D]/UGT 1A 1 *6和纯合子UGT 1A 1 *7。典型CN-2、中间组和典型GS的血清胆红素浓度分别为12.95.1、5.2 +/- 2.2和2.8 +/- 1.1mg/dL。三组间血清胆红素浓度差异有统计学意义（P
Background and Aims:Hereditary unconjugated hyperbilirubinemias, Crigler-Najjar syndrome type I, Crigler-Najjar syndrome type II (CN-2), and Gilbert syndrome (GS) all result from mutations of the bilirubin uridine 5'-diphosphate (UDP)-glucuronosyltransferase gene (UGT1A1). Often, to distinguish between CN-2 and GS is difficult because the borderline of the two syndromes is unclear. We analyzed the genotypes and phenotypes of 163 Japanese patients with CN-2 or GS.Methods:Japanese patients (99 males and 64 females) with unconjugated hyperbilirubinemia were analyzed. Their serum bilirubin concentrations varied from 1.2 to 22.2mg/dL (20 to 379M). Genetic analysis of UGT1A1 was performed by PCR-amplified direct sequencing. Association between serum bilirubin concentrations and genotypes group (typical CN-2, intermediate group, and typical GS) was studied.Results:Most patients had biallelic mutations of UGT1A1. Moreover, many of them (78.5%) had multiple mutations. The mutation in typical CN-2 was a homozygous double missense mutation of p.[G71R:Y486D]. In typical GS group, four prevalent genotypes were detected: homozygous UGT1A1*28, UGT1A1*6/UGT1A1*28, and homozygous UGT1A1*6, and UGT1A1*27/UGT1A1*28. In the intermediate group, three genotypes, p.[G71R:Y486D]/UGT1A1*7, p.[G71R:Y486D]/UGT1A1*6, and homozygous UGT1A1*7, were detected. Serum bilirubin concentrations of typical CN-2, intermediate group, and typical GS are respectively 12.95.1, 5.2 +/- 2.2, and 2.8 +/- 1.1mg/dL. Serum bilirubin concentration among the three groups is statistically different (P