尿苷二磷酸葡萄糖醛酸基转移酶1A1（UGT 1A1）Gly71Arg（G71R）基因多态性与新生儿高胆红素血症之间的关联。

Association between UGT 1A1 Gly71Arg (G71R) polymorphism and neonatal hyperbilirubinemia.

作者信息

Prachukthum Sariya, Gamnarai Pornpen, Kangsadalampai Sasichai

机构信息

Department of Pediatrics, Faculty of Medicine, Thammasat University Pathumthani, Thailand.

出版信息

J Med Assoc Thai. 2012 Jan;95 Suppl 1:S13-7.

PMID:23964438

Abstract

BACKGROUND

Neonatal hyperbilirubinemia is a common problem in neonates and affects 60% of Asian newborn babies which is twice that found in Caucasians. These findings suggest that a genetic factor might be involved. Recently, a relationship between polymorphisms of the bilirubin uridine 5-diphosphate-glucuronosyltransferase (UGTA1) gene and neonatal hyperbilirubinemia has been reported. It was demonstrated that the genetic variations cause a decrease in UGT1A1 activity in neonates, leading to an accumulation of unconjugated bilirubin in serum. However in Asians the G to A missense mutations in the UGTA1 at nucleotide 211 (known as G71R), were the predominant findings. Therefore, the impact of this polymorphism on serum bilirubin in healthy Thai neonates is of interest.

OBJECTIVE

The aim of the present study was to investigate the frequency of UGT1A1 allele in healthy Thai neonates and to determine its role in neonatal hyperbilirubinemia.

MATERIAL AND METHOD

A cross sectional study was conducted to investigate an association between the UGT1A1 G71R polymorphism and neonatal hyperbilirubinemia. Cord blood of 291 neonates was obtained to determine the gene frequency of UGT1A1 G71R by PCR-restriction fragment length polymorphism method. During the first 48 to 72 hours of the infants' life, the infants' blood was collected to measure their microbilirubin.

RESULTS

PCR-RFLP analysis revealed the UGT1A1 G71R polymorphism in 42 infants (14.4%). In addition, six of this group (14.3%) had a microbilirubin level more than 95th percentile which was approximately 2.5 times more than those with the wild type allele (5.6%). The maximum microbilirubin level of infants in the R71 allele group was significantly higher than those in the G71 allele group, (11.79 +/- 3.34 mg/dL and 9.53 +/- 2.34 mg/dL, respectively p < 0.01).

CONCLUSION

In the present study, the UGT1A1 G71R allele was found to be one of the risk factors for neonatal hyperbilirubinemia in Thai neonates.

摘要

背景

新生儿高胆红素血症是新生儿中的常见问题，影响60%的亚洲新生儿，这一比例是白种人的两倍。这些发现表明可能涉及遗传因素。最近，有报道称胆红素尿苷5 - 二磷酸 - 葡萄糖醛酸基转移酶（UGTA1）基因多态性与新生儿高胆红素血症之间存在关联。已证实基因变异导致新生儿UGT1A1活性降低，从而导致血清中未结合胆红素的积累。然而在亚洲人中，UGTA1基因第211位核苷酸处的G到A错义突变（称为G71R）是主要发现。因此，这种多态性对健康泰国新生儿血清胆红素的影响备受关注。

目的

本研究旨在调查健康泰国新生儿中UGT1A1等位基因的频率，并确定其在新生儿高胆红素血症中的作用。

材料与方法

进行了一项横断面研究，以调查UGT1A1 G71R多态性与新生儿高胆红素血症之间的关联。采集291例新生儿的脐带血，通过聚合酶链反应 - 限制性片段长度多态性方法确定UGT1A1 G71R的基因频率。在婴儿出生后的头48至72小时内，采集婴儿血液以测量其微量胆红素。

结果

聚合酶链反应 - 限制性片段长度多态性分析显示42例婴儿（14.4%）存在UGT1A1 G71R多态性。此外，该组中有6例（14.3%）的微量胆红素水平超过第95百分位数，这大约是野生型等位基因婴儿（5.6%）的2.5倍。R71等位基因组婴儿的最高微量胆红素水平显著高于G71等位基因组婴儿，分别为（11.79±3.34mg/dL和9.53±2.34mg/dL，p<0.01）。