Yang Hui, Wang Qian, Zheng Lei, Zheng Xiang-Bin, Lin Min, Zhan Xiao-Fen, Yang Li-Ye
Laboratory Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, PR China; Central Laboratory, Chaozhou Central Hospital Affiliated to Southern Medical University, Chaozhou, Guangdong Province, PR China.
Laboratory Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, PR China.
Pediatr Neonatol. 2016 Aug;57(4):310-7. doi: 10.1016/j.pedneo.2015.08.008. Epub 2015 Dec 2.
Neonatal hyperbilirubinemia is common in Asia, and the importance of genetically determined conditions has been recently recognized. The aim of this study was to assess the clinical utility of genetic testing in Chinese neonates with severe hyperbilirubinemia.
Fifty-eight term infants with bilirubin level ≥ 20 mg/dL (342 μmol/L), and 65 controls were enrolled in the study. Variation status of UGT1A1, G6PD, and thalassemia genes in our study cohort was determined by direct sequencing or genotype assays.
Among these case infants, seven were confirmed with G6PD deficiency, four were heterozygous for α- or β-thalassemia, and forty-four were detected with at least one heterozygous UGT1A1 functional variant, including nine homozygous for UGT1A1 variation. As well as the predominant c.211G>A (Gly71Arg) variant, three UGT1A1 coding variants [c.1091C>T (Pro364Leu), c.1352C>T (pro451leu), and c.1456C>T (Tyr486Asp)] were observed in our case neonates. The results of multivariate logistic regressions, adjusted for covariates, revealed odds ratios for neonates who carried heterozygous, homozygous variation at nucleotide 211 of UGT1A1, and G6PD deficiency of 3.47 (1.26-9.55), 12.46 (1.09-142.7) ,and 12.87 (1.32-135.87) compared with those having the wild genotype and normal G6PD activity, respectively.
Besides G6PD-deficiency screening, UGT1A1 genetic analysis, and especially the UGT1A1*6(c.211G>A, p.Arg71Gly) polymorphism detection, may be taken into consideration for early diagnosis and treatment of severe hyperbilirubinemic newborns in southern China.
新生儿高胆红素血症在亚洲很常见，近年来人们已经认识到基因决定因素的重要性。本研究的目的是评估基因检测在中国重度高胆红素血症新生儿中的临床应用价值。
本研究纳入了58名足月婴儿，其胆红素水平≥20mg/dL（342μmol/L），并选取了65名对照。通过直接测序或基因分型检测确定研究队列中UGT1A1、G6PD和地中海贫血基因的变异状态。
在这些病例婴儿中，7例确诊为G6PD缺乏，4例为α或β地中海贫血杂合子，44例检测到至少一种UGT1A1功能变异杂合子，其中9例为UGT1A1变异纯合子。除了主要的c.211G>A（Gly71Arg）变异外，在我们的病例新生儿中还观察到三种UGT1A1编码变异[c.1091C>T（Pro364Leu）、c.1352C>T（pro451leu）和c.1456C>T（Tyr486Asp）]。多因素逻辑回归结果经协变量调整后显示，与野生基因型和G6PD活性正常的新生儿相比，UGT1A1第211位核苷酸携带杂合、纯合变异以及G6PD缺乏的新生儿的比值比分别为3.47（1.26 - 9.55）、12.46（1.09 - 142.7）和12.87（1.32 - 135.87）。
在中国南方，对于重度高胆红素血症新生儿的早期诊断和治疗，除了进行G6PD缺乏筛查外，还可考虑进行UGT1A1基因分析，尤其是UGT1A1*6（c.211G>A，p.Arg71Gly）多态性检测。
