Azlin I, Wong F L, Ezham M, Hafiza A, Ainoon O
Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
Malays J Pathol. 2011 Dec;33(2):95-100.
A number of genetic risk factors have been implicated in the development of neonatal severe hyperbilirubinaemia. This includes mutations in the uridine glucoronosyl transferase 1A1 (UGT1A1) gene which is responsible for unconjugated hyperbilirubinemia in Gilbert's Syndrome. We studied the prevalence of UGT1A1 gene mutations in a group of Malay neonates to determine whether they are risk factors to severe neonatal jaundice. One hundred and twenty-five Malay neonates with severe hyperbilirubinemia were studied. Ninety-eight infants without severe hyperbilirubinaemia were randomly selected from healthy Malay term infants (controls). DNA from EDTA cord blood samples were examined for UGT1A1 mutations nt211G > A and nt247T > C using established Taqman SNP genotyping assays and the UGT1A128 variant was detected by the Agilent 2100 bioanalyzer. All samples were also screened for common Malay G6PD variants using established techniques. The frequency of UGT1A1 211G > A mutation is significantly higher in the severely hyperbilirubinemic group (13%) than the control group (4%; p = 0.015) and all the positive cases were heterozygous for the mutation. There was no significant difference in the frequency of UGT1A128 mutation between the severely hyperbilirubinemic (3.5%) and the control group (0.01%; p = 0.09). None of the neonates in both groups carried the nt247 T > C mutation. The prevalence of G6PD mutation was significantly higher in the severely jaundiced group than control (9% vs 4%; p = 0.04). In conclusion, nt 211 G > A alleles constitute at least 12% of UGT1A1 mutations underlying unconjugated hyperbilirubinemia and appears to be a significant independent risk factor associated with severe neonatal hyperbilirubinemia in the Malay newborns.
许多遗传风险因素与新生儿严重高胆红素血症的发生有关。这包括尿苷葡萄糖醛酸基转移酶1A1（UGT1A1）基因突变，该基因与吉尔伯特综合征中的非结合性高胆红素血症有关。我们研究了一组马来新生儿中UGT1A1基因突变的患病率，以确定它们是否是严重新生儿黄疸的风险因素。对125名患有严重高胆红素血症的马来新生儿进行了研究。从健康的马来足月儿（对照组）中随机选取98名无严重高胆红素血症的婴儿。使用既定的Taqman SNP基因分型检测法检测EDTA脐带血样本中的DNA是否存在UGT1A1突变nt211G>A和nt247T>C，并通过安捷伦2100生物分析仪检测UGT1A128变体。还使用既定技术对所有样本进行常见马来G6PD变体筛查。严重高胆红素血症组中UGT1A1 211G>A突变的频率（13%）显著高于对照组（4%；p=0.015），所有阳性病例均为该突变的杂合子。严重高胆红素血症组（3.5%）和对照组（0.01%；p=0.09）之间UGT1A128突变的频率无显著差异。两组新生儿均未携带nt247 T>C突变。严重黄疸组中G6PD突变的患病率显著高于对照组（9%对4%；p=0.04）。总之，nt 211 G>A等位基因构成了非结合性高胆红素血症中UGT1A1突变的至少12%，似乎是马来新生儿严重新生儿高胆红素血症的一个重要独立风险因素。
