胆红素尿苷二磷酸葡萄糖醛酸转移酶多态性与新生儿黄疸

尿苷二磷酸葡萄糖醛酸转移酶(UDP-glucurono-syltransferase,UGT)是一大类能催化葡萄糖醛酸与亲核底物结合的酶家族,主要存在于肝脏,与微粒体膜相结合,催化肝脏生物转化作用第二相反应中葡萄糖醛酸结合反应。UGT家族包括30多个成员,按其序列的相似性,可将UGT分为两大亚家族,即U     

新生儿黄疸与胆红素-尿苷二磷酸葡萄糖醛酸转移酶和有机阴离子转运因子2基因突变的关系

目的探讨胆红素-尿苷二磷酸葡萄糖醛酸转移酶(UGT1A1)基因Gly71Arg突变和有机阴离子转运因子2(OATP2)基因Asn130Asp突变与新生儿黄疸发病的关系。方法应用聚合酶链反应-限制性长度多态性方法测定无亲缘关系的汉族新生儿黄疸组与健康对照组的UGT1A1Gly71Arg和OATP2Asn130Asp基因多态性的基因型,并检验两组基因型分布、等位基因频率差异,应用Logistic多元回归分析两种基因突变对新生儿黄疸的OR值和95%CI。结果新生儿黄疸组UGT1A1Gly71Arg和OATP2Asn130Asp基因多态性的基因型分布与对照组差异有统计学意义(χ2=9.47和6.16,P=0.002和0.046),Arg和Asp等位基因频率明显高于对照组(χ2=10.34和6.85,P=0.001和0.009);logistic多元回归分析UGT1A1基因Gly71Arg和OATP2基因Asn130Asp突变对新生儿黄疸的OR值和95%CI分别为2.66(1.38~4.51)和2.32(1.23~3.95)(P=0.011和0.024)。结论UGT1A1基因Gly71Arg和OATP2基因Asn130Asp突变可能参与新生儿黄疸的发病。     

新生儿黄疸与胆红素-尿苷二磷酸葡萄糖醛酸转移酶和有机阴离子转运因子2基因突变的关系

目的 探讨胆红素-尿苷二磷酸葡萄糖醛酸转移酶（UGT1A1）基因Gly71Arg突变和有机阴离子转运因子2（OATP2）基因Asn130Asp突变与新生儿黄疸发病的关系。方法应用聚合酶链反应-限制性长度多态性方法测定无亲缘关系的汉族新生儿黄疸组与健康对照组的UGT1A1Gly71Arg和OATP2Asn130Asp基因多态性的基因型,并检验两组基因型分布、等位基因频率差异,应用Logistic多元回归分析两种基因突变对新生儿黄疸的OR值和95%CI。结果 新生儿黄疸组UGT1A1Gly71Arg和OATP2Asn130Asp基因多态性的基因型分布与对照组差异有统计学意义（χ^2=9.47和6.16,P=0.002和0.046）,Arg和Asp等位基因频率明显高于对照组（χ^2=10.34和6.85,P=0.001和0.009）;logistic多元回归分析UGT1A1基因Gly71Arg和OATP2基因Asn130Asp突变对新生儿黄疸的OR值和95%CI分别为2.66（1.38～4.51）和2.32（1.23～3.95）（P=0.011和0.024）。结论 UGT1A1基因Gly71Arg和OATP2基因Asn130Asp突变可能参与新生儿黄疸的发病。     

Relationship between bilirubin UDP-glucuronosyl transferase 1A1 gene and neonatal hyperbilirubinemia

The variation rate within the coding region of UDP-glucuronosyl transferase 1A1 (UGT1A1) gene in Taiwan Chinese was found to be 29.3%. This study sought to determine whether that high variation rate of UGT1A1 gene is a risk factor for neonatal hyperbilirubinemia. The study subjects consisted of 123 newborn infants suffering from unconjugated hyperbilirubinemia who had no known risk factors for hyperbilirubinemia and 218 healthy control neonates. The promoter area, exons 1 to 4, coding region of exon 5, and the flanking intronic regions in UGT1A1 gene were determined by the PCR in all subjects. Wild UGT1A1 gene, variation in the promoter, variation at nucleotide 211, variation at nucleotide 1091, and compound heterozygous variation of UGT1A1 gene were found. The percentage of neonates with wild UGT1A1 gene and the percentage of neonates with variation at nucleotide 211 were significantly different between the study subjects and controls. The percentages with bilirubin >or=342 micro M (20.0 mg/dL) and with persistent hyperbilirubinemia in the subjects carrying homozygous variation at nucleotide 211 (Gly71Arg) were significantly higher than the neonates carrying wild type or other genotypes. In conclusion, this study has demonstrated that variation at nucleotide 211 of the UGT1A1 gene is a risk factor for the development of neonatal hyperbilirubinemia. Pediatricians should closely follow hyperbilirubinemic newborn infants who carry homozygous 211 G to A variation in UGT1A1 gene.     

尿苷二磷酸葡萄糖醛酸转移酶1A1基因与新生儿黄疸

尿苷二磷酸葡萄糖醛酸转移酶（UGT）是胆红素结合的关键酶,此酶的缺陷使胆红素不能与葡萄糖醛酸结合形成结合胆红素,使非结合胆红素在体内堆积,导致Crigler—Najjiar综合征（包括Ⅰ型、Ⅱ型）和Gilbert综合征。CN—Ⅰ型患儿由于高度缺乏UGT,生后1～2d即出现严重黄疸,血清间接胆红素可达256．5～595．0μnaol／L,苯巴比妥治疗无效,需换血与光疗结合,常见短期内出现胆红素脑病,多在新生儿期和婴儿期死亡,属常染色体隐性遗传。CN—Ⅱ型为UGT活性缺陷,但并非完全缺乏,可表现为新生儿期较轻的黄疸,但也可发生严重的高胆红素血症和核黄疸。血清间接胆红素浓度一般在85—340μmol／L,苯巴比妥治疗有效,属常染色体显性遗传。Gilbert综合征为一种轻度的慢性高间接胆红素血症,系由肝脏摄取胆红素缺陷和UGT活性降低所致,通常于青春期才症状明显,给苯巴比妥能降低总胆红素值,是一种常染色体显性遗传病。     

A prolonged neonatal jaundice associated with a rare G6PD mutation

Glucose‐6‐phosphate dehydrogenase (G6PD), a X‐linked hereditary deficiency, is one of most common clinically significant enzyme defects. Despite its largely known role in acute and life‐threatening haemolytic crises, G6PD deficiency may be also associated with neonatal jaundice that, when severe and untreated, may lead to the potential of bilirubin encephalopathy. A prolonged neonatal jaundice was found to be associated with a rare G6PD mutation (c.383T>G; p.L128R), the latter simply annotated in literature database. In this article, we clinically and phenotipically describe a case of an Italian neonate carrying the c.383T>G G6PD mutation. Finally, we named this variant “G6PD Salerno.” Pediatr Blood Cancer 2009;53:475–478. © 2009 Wiley‐Liss, Inc.     

UGT1A1 G71R 基因多态性对母乳性黄疸程度的影响

目的探讨葡萄糖醛酸转移酶UGT1A1 G71R基因突变对晚发型母乳性黄疸患儿黄疸程度的影响。方法收集晚发型母乳性黄疸患儿56例,用套式PCR后限制性片段长度多态性分析(RFLP)确定UGT1A1 G71R基因型,通过全自动生化分析仪测定胆红素水平。结果UGT1A1 G71R突变纯合子5例,杂合子24例,野生型27例。UGT1A1 G71R等位基因频率为30.36%。UGT1A1 G71R纯合子或杂合子组(n=29)与UGT1A1G71R野生组(n=27)的胆红素水平分别为(237.85±31.92)μmol/L、(214.49±32.48)μmol/L,前者明显高于后者(t=2.7141,P=0.0089)。结论晚发型母乳性黄疸患儿如存在UGT1A1 G71R基因突变,临床上黄疸程度较重。     

有机阴离子转运体1B1基因与新生儿黄疸关系的研究进展

有机阴离子转运体2(OATP2)是一种肝细胞膜上转运胆红素等物质的转运体,影响胆红素的代谢.OATP2 由有机阴离子转运体1B1(SLCO1B1)基因编码,该基因突变可抑制OATP2 的转运功能,致胆红素清除减慢,引起高胆红素血症.近年的研究显示,SLCO1B1 基因多态性可能与新生儿黄疸发生相关.该文综述了SLCO1B1 基因结构、功能及SLCO1B1 基因突变与新生儿黄疸的关系.     

基因多态性与新生儿迁延性黄疸研究进展

部分新生儿黄疸患儿可出现迁延性黄疸,黄疸消退延迟,可持续2~3个月。其严重并发症为核黄疸,表现为不可逆的神经系统损伤,故新生儿黄疸已成为全球关注的问题。目前新生儿迁延性黄疸的发病机制尚不明确,近年来研究发现,遗传因素与新生儿迁延性黄疸密切相关,该文就常见的基因多态性与新生儿迁延性黄疸的研究进展进行综述。     

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目的探讨葡萄糖醛酸转移酶1A1(UGT1A1)基因G71R突变、葡萄糖-6-磷酸脱氢酶(G6PD)缺陷对新生儿生后前3d胆红素浓度的影响.方法测定81例新生儿脐血的G6PD活性及G71R基因型,分组比较生后前3d光疗前胆红素值的组间差异.用等位基因特异性寡核苷酸探针点杂交法(ASO)确定G71R基因型.结果在G71R野生型新生儿中,G6PD缺乏组与G6PD正常组相比,生后前3d胆红素值间无统计学差异.G6PD正常新生儿中,G71R突变纯合子或杂合子的新生儿生后前3d胆红素浓度与G71R正常野生型新生儿相比无统计学差异.G6PD缺陷新生儿中,同时合并有G71R突变纯合子或杂合子的新生儿组生后第2天、第3天胆红素浓度高于G71R正常野生型新生儿组.结论G6PD缺乏与G71R基因突变并存加重新生儿黄疸程度.     

新生儿高胆红素血症与有机阴离子转运体1B1 T521C/A388G多态性的相关性研究

目的 有机阴离子转运体1B1(OATP 1B1)跨膜转运体内非结合胆红素(UCB),其基因变异能显著影响体内胆红素水平.此课题即为研究OATP 1B1基因多态性与新生儿高胆红素血症的相关性.方法 用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)方法分析220例高胆红素血症新生儿及200名对照者OATP 1B1 T521/A388G基因型,观察基因突变频率及基因型分布、基因多态性与疾病的相关性及对患儿血清总胆红素、结合胆红素、非结合胆红素水平的影响.结果 在高胆红素血症新生儿中,OATP 1B1 T521C等位基因突变频率显著下降,仅为8.2%.野生型的患者比例要显著高于对照组中野生型个体比例,达到84.1%.携带C等位基因的个体患病风险下降(OR=0.530,95%CI=0.328～0.857).血清总胆红素、结合胆红素、非结合胆红素水平在OATP 1B1A388G野生型患者中最高,杂合子次之,突变纯合子最低.结论 OATP 1B1 T521C多态性在新生儿高胆红素血症患儿中存在明显差异,OATP 1B1 A388G多态性显著影响新生儿高胆红素血症患儿血清胆红素水平.OATP 1B1 T521C/A388G是和新生儿高胆红素血症相关的重要基因多态位点.     

UGT1A1 TATA基因突变与新生儿高胆红素血症的关系

新生儿高未结合胆红素血症是一种常见病,我国南方葡萄糖-6-磷酸脱氢酶（G-6-PD）缺陷致新生儿黄疸临床多见。东亚人、同胞兄弟姐妹中有黄疸史及家族中有黄疸史者发病率高等危险因素均提示遗传因素在新生儿黄疸发病中有一定作用。近年来,不少学者提出葡萄糖醛酸转移酶基因缺陷是新生儿黄疸的重要发病机制之一,G-6-PD缺陷与葡萄糖醛酸转移酶基因突变对新生儿黄疸发病存在协同作用。现就新生儿高胆红素血症发病中遗传因素的新进展作一综述。     

Prolonged neonatal jaundice: When to worry and what to do

Neonatal jaundice persisting beyond 14 days of age is a common clinical scenario. The vast majority of affected children have a benign unconjugated hyperbilirubinemia, but included in this clinical presentation is a group of neonates with conjugated hyperbilirubinemia and liver disease. Early identification of liver disease improves the infant’s outcome, especially for those with extrahepatic biliary atresia. The present paper reviews the approach to the neonate with prolonged jaundice, including clinical presentation, when to proceed with initial investigations, timing of referral, further investigations and management, and provides an overview of the more common causes of neonatal cholestatic liver disease.     

A new device for phototherapy of neonatal jaundice]

The effectiveness of a new device for phototherapy in the treatment of nonhemolytic hyperbilirubinemia (Wallaby Phototherapy System) was evaluated. 46 healthy term infants, appropriate for gestational age and with serum bilirubin > 12 mg/dl in the first 3 days of life or > 15 mg/dl after 3rd day were randomly assigned to a treatment group (24 hours of light exposure with Wallaby Phototherapy System) and to a control group (any treatment for hyperbilirubinemia). Body temperature, weight, feeding and hydration were recorded during the study period. Serum bilirubin and haematocrit were done every 12 hours in all babies. In the treated group we found a decrease of 5.1% and of 7.8% at 12 and 24 hours, while an increase of 3.37% and of 2.9% at 12 and 24 hours was found in the control group. After 24 hours the serum bilirubin level was significantly lower in the treated group than in the control group (p < 0.05). No newborn of the treated group needed conventional phototherapy versus 4 control infants (17.4%). The conclusion of our study is that the Wallaby System is useful in the treatment of neonatal nonhemolytic hyperbilirubinemia even if its effectiveness for higher bilirubin levels has still to be tested.