The Role of Heme Oxygenase-1 Promoter Polymorphisms in Perinatal Disease

• Main Authors: Ruka Nakasone, Mariko Ashina, Shinya Abe, Kenji Tanimura, Hans Van Rostenberghe, Kazumichi Fujioka
• Format: Article
• Language: English
• Published: MDPI AG 2021-03-01
• Series: International Journal of Environmental Research and Public Health
• Subjects: heme oxygenase-1; polymorphism; perinatal diseases; neonatal jaundice; genetics; SNPs
• Online Access: https://www.mdpi.com/1660-4601/18/7/3520
• ISSN: 1661-7827; 1660-4601

Heme oxygenase (HO) is the rate-limiting enzyme in the heme catabolic pathway, which degrades heme into equimolar amounts of carbon monoxide, free iron, and biliverdin. Its inducible isoform, HO-1, has multiple protective functions, including immune modulation and pregnancy maintenance, showing dynamic alteration during perinatal periods. As its contribution to the development of perinatal complications is speculated, two functional polymorphisms of the <i>HMOX1</i> gene, (GT)_n repeat polymorphism (rs3074372) and A(-413)T single nucleotide polymorphism (SNP) (rs2071746), were studied for their association with perinatal diseases. We systematically reviewed published evidence on <i>HMOX1</i> polymorphisms in perinatal diseases and clarified their possible significant contribution to neonatal jaundice development, presumably due to their direct effect of inducing HO enzymatic activity in the bilirubin-producing pathway. However, the role of these polymorphisms seems limited for other perinatal complications such as bronchopulmonary dysplasia. We speculate that this is because the antioxidant or anti-inflammatory effect is not directly mediated by HO but by its byproducts, resulting in a milder effect. For better understanding, subtyping each morbidity by the level of exposure to causative environmental factors, simultaneous analysis of both polymorphisms, and the unified definition of short and long alleles in (GT)_n repeats based on transcriptional capacity should be further investigated.