UGT1A1基因G71R突变与新生儿不明原因严重高胆红素血症相关

G71R mutation of the UGT1A1 gene is associated with severe neonatal hyperbilirubinemia with unknown etiology

目的探讨尿苷二磷酸葡萄糖醛酸转移酶1A1（UGT1A1）基因G71R突变与新生儿严重高胆红素血症的相关性.方法采用病例对照研究的方法,病例组为复旦大学附属儿科医院（我院）收治的不明原因严重高胆红素血症（血清总胆红素水平≥342μmol·L^-1）新生儿,采用PCR对外周血UGT1A1基因进行检测.对照组为我院新生儿出生缺陷生物样本数据库中血清总胆红素水平〈221μmol·L^-1病例.病例组及对照组新生儿均要求胎龄≥35周,出生体重≥2500g.结果病例组和对照组各65例.UGT1A1G71R是病例组中最常见的突变类型（73.8%,48/65）.对照组UGT1A1G71R突变位点与既往Meta分析中提取的中国健康新生儿对比,在基因型分布及等位基因频率上差异均无统计学意义（P〉005）.病例组和对照组UGT1A1基因G71R突变中A等位基因频率分别为0.5和0.15,差异有统计学意义（P〈0.001）,把握度为0.993.与携带G/G基因型新生儿相比,UGT1A1G71R突变（A/A＋G/A基因）可增加新生儿严重高胆红素血症的发病风险（OR=7.373,95%CI3.395～16.008）,把握度为1.0.结论UGT1A1基因G71R突变与新生儿不明原因严重高胆红素血症相关.

Objective To assess whether G71 R mutation of the UGT1A1 gene is associated with severe neonatal hyperbilirubinemia of unknown cause. M ethods In a case-control study performed at a single hospital center in China,cases with severe hyperbilirubinemia( defined as bilirubin level≥342 μmol·L- 1) and controls from neonatal birth defects samples database( bilirubin level < 221 μmol·L- 1) were enrolled. Polymerase chain reaction analysis of blood was performed to determine the frequency of UGT1A1 mutation in cases. All subjects were born with gestational age ≥ 35 weeks and birth weight ≥ 2500 g.Results A total of 65 severe hyperbilirubinemic neonates and 65 control neonates were enrolled into the study. UGT1A1 G71 R was the most common mutation in cases( 48 /65). No statistical difference in the genotype or 211 G to A allele frequencies was found between controls and Chinese healthy infants from a meta-analysis( P > 0. 05). The allelic frequency of ' A' in G71 R was 0. 5 in severe hyperbilirubinemic neonates,which was significantly higher than 0. 15 in the control group( P < 0. 001),power was 0. 993.The genotype frequency of ' A / A + G / A' was 73. 8% in severe hyperbilirubinemic neonates,which was significantly higher than 27. 7% in the control group( P < 0. 001),power was 1. The result revealed that the G71 R mutant carriers( A / A + G / A) were associated with an increased risk of severe neonatal hyperbilirubinemia compared with the G / G allele carriers( OR = 7. 373,95% CI: 3. 395- 16. 008) Conclusion This finding strongly suggests that the presence of the G71 R mutation contributes to the development of neonatal severe hyperbilirubinemia of unknown etiologyin the Chinese population.