Katayama Yoshinori, Yokota Tomoyuki, Zhao Hui, Wong Ronald J, Stevenson David K, Taniguchi-Ikeda Mariko, Nakamura Hajime, Iijima Kazumoto, Morioka Ichiro
Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
Department of Pediatrics, Takatsuki General Hospital, Takatsuki, Japan.
Pediatr Int. 2015 Aug;57(4):645-9. doi: 10.1111/ped.12591. Epub 2015 Apr 28.
Heme oxygenase (HO) is the rate-limiting enzyme in the heme degradation pathway that produces bilirubin. The promoter region of human heme oxygenase-1 (HMOX1) contains a polymorphic (GT)n repeat that can regulate gene expression. Here, we investigated the association of (GT)n repeat length in the HMOX1 promoter region with neonatal hyperbilirubinemia in a population of Japanese term neonates.
Using polymerase chain reaction and fragment analysis, we determined the number of (GT)n repeats in 149 Japanese neonates. To omit the effects of the G71R mutation in uridine diphosphoglucuronosyltransferase on hyperbilirubinemia, we excluded 41 neonates with the G71R mutation. As a result, 25 neonates with hyperbilirubinemia and 83 non-hyperbilirubinemic controls were included in this prospective case-control study. Allele and genotype frequencies of (GT)n repeats in the HMOX1 gene were compared between hyperbilirubinemic and non-hyperbilirubinemic control neonates.
The prevalence of short alleles (< 22 (GT)n repeats) was significantly higher in hyperbilirubinemic than in control neonates (18% vs 7%, P = 0.015). Hyperbilirubinemia was more frequent in homozygous or heterozygous short allele carriers than control neonates (28% vs 11%, respectively, P = 0.03). Possession of short alleles was significantly associated with the development of neonatal hyperbilirubinemia (OR, 3.1; 95%CI: 1.03-9.53).
Infants carrying short alleles (< 22 (GT)n repeats) in the HMOX1 gene promoter region appear to be at a higher risk for developing neonatal hyperbilirubinemia.
血红素加氧酶（HO）是血红素降解途径中产生胆红素的限速酶。人血红素加氧酶-1（HMOX1）的启动子区域包含一个多态性（GT）n重复序列，其可调节基因表达。在此，我们在一群日本足月儿中研究了HMOX1启动子区域（GT）n重复序列长度与新生儿高胆红素血症的关联。
我们使用聚合酶链反应和片段分析，确定了149名日本新生儿中（GT）n重复序列的数量。为排除尿苷二磷酸葡萄糖醛酸转移酶中G71R突变对高胆红素血症的影响，我们排除了41名携带G71R突变的新生儿。结果，本前瞻性病例对照研究纳入了25名高胆红素血症新生儿和83名非高胆红素血症对照。比较了高胆红素血症和非高胆红素血症对照新生儿中HMOX1基因（GT）n重复序列的等位基因和基因型频率。
短等位基因（<22个（GT）n重复序列）在高胆红素血症新生儿中的患病率显著高于对照新生儿（18%对7%，P = 0.015）。纯合或杂合短等位基因携带者中高胆红素血症的发生率高于对照新生儿（分别为28%对11%，P = 0.03）。携带短等位基因与新生儿高胆红素血症的发生显著相关（OR，3.1；95%CI：1.03 - 9.53）。
在HMOX1基因启动子区域携带短等位基因（<22个（GT）n重复序列）的婴儿似乎发生新生儿高胆红素血症的风险更高。
