BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSION 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.

中文翻译：

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印度尼西亚后马来人群新生儿高胆红素血症的 G6PD 遗传变异。

背景技术新生儿黄疸是亚洲（包括印度尼西亚）新生儿的常见症状。在某些情况下，血清总胆红素水平超过生命中第 95 个百分位（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。多项研究已报道 6-磷酸葡萄糖脱氢酶 (G6PD) 遗传变异和缺陷与 NH 相关。本研究旨在分析印度尼西亚中马来人人群中患有和不患有高胆红素血症的新生儿中 G6PD 遗传变异及其活性。方法从116例和115例患有和不患有高胆红素血症的健康足月新生儿的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、Coombs试验、使用Randox试剂盒方法测量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 进行了 G6PD 多态性与 NH 的关联研究。结果 印度尼西亚后马来族人群中，患有和不患有高胆红素血症的新生儿中 G6PD 缺乏症的患病率分别为 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.1365-13 T/IVS11。然而，这些多态性及其单倍型均与 NH 无关（p > 0.05，比值比 (OR) ~1.00）。有和没有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%)。最常见的 G6PD 突变是 Viangchan 变体 (p.V291 M)，其次是 Canton (p.R459L) 和 Vanua Lava (p.L128P) 变体。在病例组（p.V369A、p.I167F）和对照组（p.L474=、p.I36T）中均发现了两个新突变。结论 在印度尼西亚中马来语人群中，无论是否患有高胆红素血症，新生儿 G6PD 缺乏症的患病率均较低。本研究中在印度尼西亚后马来语群体中发现的大多数 G6PD 突变是 Viangchan、Canton 和 Vanua Lava 变体。