Wisnumurti Dewi A, Sribudiani Yunia, Porsch Robert M, Maskoen Ani M, Rahayuningsih Sri E, Asni Eni K, Sleutels Frank, van Ijcken Wilfred F J, Sukadi Abdurachman, Achmad Tri H
Departement of Pediatric, Neonatology Subdivision, Arifin Achmad General Hospital, Universitas Riau, Pekanbaru, Indonesia.
Research Center of Medical Genetics, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia.
BMC Pediatr. 2019 Dec 20;19(1):506. doi: 10.1186/s12887-019-1882-z.
Neonatal jaundice is a common finding in newborns in Asia, including Indonesia. In some cases, the serum total bilirubin levels exceeds the 95th percentile for hours of life (neonatal hyperbilirubinemia). Severe neonatal hyperbilirubinemia (NH) could lead to kernicterus and neonatal death. Glucose-6-Phosphage Dehydrogenase (G6PD) genetic variations and deficiency have been reported in several studies to be associated with NH. This study aimed to analyze the G6PD genetic variations and its activity in neonates with and without hyperbilirubinemia in the Deutromalay Indonesian population.
Deoxyribose Nucleic Acid (DNA) was isolated from peripheral blood of 116 and 115 healthy term neonates with and without hyperbilirubinemia. All infants underwent the following laboratory examinations: routine hematologic evaluation, Coombs test, G6PD activity measurement using the Randox kit method, and serum total bilirubin level. All exons of the G6PD gene were targeted for deep sequencing using MiSeq (Illumina). An association study of G6PD polymorphisms with NH was performed using PLINK.
The prevalence of G6PD deficiency in neonates with and without hyperbilirubinemia in Indonesian Deutromalay population were 1.72% (95% Confidence Interval (CI): 0.6-4.1%) and 1.74% (95% CI: 0.7-4.1%), respectively. The most common G6PD polymorphisms, i.e. rs1050757/c.* + 357A > G, rs2230037/c.1311C > T, and rs2071429/c.1365-13 T/IVS11, were identified. However, none of those polymorphisms and their haplotype were associated with NH (p > 0.05, Odds Ratio (OR) ~1.00). The prevalence of G6PD mutations in neonates with and without hyperbilirubinemia were 6.8% (95% CI: 2.3-11.5%) and 6.9% (95% CI: 2.3-11.6%), respectively. The most frequently identified G6PD mutation was the Viangchan variant (p.V291 M), which was followed by the Canton (p.R459L) and Vanua Lava (p.L128P) variants. Two novel mutations were identified both in case (p.V369A, p.I167F) and control (p.L474=, p.I36T) groups.
The prevalence of G6PD deficiency is low in neonates with or without hyperbilirubinemia in Deutromalay Indonesian population. The majority of G6PD mutations identified among Indonesian Deutromalay population in this study are Viangchan, Canton and Vanua Lava variants.
新生儿黄疸在包括印度尼西亚在内的亚洲新生儿中很常见。在某些情况下，血清总胆红素水平在出生后数小时内超过第95百分位数（新生儿高胆红素血症）。严重的新生儿高胆红素血症（NH）可能导致核黄疸和新生儿死亡。多项研究报道，葡萄糖-6-磷酸脱氢酶（G6PD）基因变异和缺乏与NH有关。本研究旨在分析德特罗马莱印尼人群中患高胆红素血症和未患高胆红素血症的新生儿的G6PD基因变异及其活性。
从116名患高胆红素血症和115名未患高胆红素血症的健康足月儿外周血中分离脱氧核糖核酸（DNA）。所有婴儿均接受以下实验室检查：常规血液学评估、库姆斯试验、使用朗道试剂盒法测量G6PD活性以及血清总胆红素水平。使用MiSeq（Illumina）对G6PD基因的所有外显子进行深度测序。使用PLINK对G6PD多态性与NH进行关联研究。
在印尼德特罗马莱人群中，患高胆红素血症和未患高胆红素血症的新生儿中G6PD缺乏的患病率分别为1.72%（95%置信区间（CI）：0.6 - 4.1%）和1.74%（95%CI：0.7 - 4.1%）。鉴定出最常见的G6PD多态性，即rs1050757/c.* + 357A > G、rs2230037/c.1311C > T和rs2071429/c.1365 - 13T/IVS11。然而，这些多态性及其单倍型均与NH无关（p > 0.05，优势比（OR）约为1.00）。患高胆红素血症和未患高胆红素血症的新生儿中G6PD突变的患病率分别为6.8%（95%CI：2.3 - 11.5%）和6.9%（95%CI：2.3 - 11.6%）。最常鉴定出的G6PD突变是万象变体（p.V291M），其次是广州（p.R459L）和瓦努阿·拉瓦（p.L128P）变体。在病例组（p.V369A，p.I167F）和对照组（p.L474 =，p.I36T）中均鉴定出两个新突变。
在印尼德特罗马莱人群中，患或未患高胆红素血症的新生儿中G6PD缺乏的患病率较低。本研究在印尼德特罗马莱人群中鉴定出的大多数G6PD突变是万象、广州和瓦努阿·拉瓦变体。
