Association between genetic polymorphism of heme oxygenase 1 promoter and neonatal hyperbilirubinemia: a meta-analysis

Objective: The association between a (GT)(n) dinucleotide length polymorphism in the promoter region of heme oxygenase 1 (HMOX1) and the risk of neonatal hyperbilirubinemia remains controversial. This meta-analysis was, therefore, performed with aims to examine the correlation between the HMOX1 (GT)(n) repeat length polymorphism and neonatal hyperbilirubinemia susceptibility.Materials and methods: We searched the databases including PubMed, Embase, Cochrane Library, China national knowledge infrastructure (CNKI), and Wanfang Data, with all reviewed studies published before 28 June 2018. After the evaluation of quality, we used RevMan to perform the meta-analyses. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the effect of HMOX1 gene promoter polymorphisms on the risk of neonatal hyperbilirubinemia.Results: Seven studies, involving 584 patients with neonatal hyperbilirubinemia and 1655 controls, were included. A statistically significant association was found between the HMOX1 (GT)(n) repeat length polymorphism and risk of neonatal hyperbilirubinemia under the allele (allele S vs. allele L: OR=1.81, 95% CI=1.22-2.67, p=.003), recessive (genotype SS vs. genotypes LS+LL: OR=1.38, 95% CI=1.02-1.86, p=.04), dominant (genotypes SS+LS vs. LL: OR=1.37, 95% CI=1.01-1.76, p=.01), and homozygous genetic models (genotype SS vs. genotype LL: OR=1.47, 95% CI=1.02-2.11, p=.003), but not under the heterozygous genetic model. Interestingly, subgroup analysis revealed that the cutoffs of the S allele < 25 showed significant associations in any of the five genetic models (allele S vs. allele L: OR=2.26, 95% CI=1.68-3.05, p<.00001; genotype SS vs. genotypes LS+LL: OR=2.56, 95% CI=1.41-4.65, p=.002; genotypes SS+LS vs. genotype LL: OR=1.82, 95% CI=1.28-2.59, p=.0009; genotype SS vs. genotype LL: OR=3.09, 95% CI=1.50-6.36, p=.002; genotype LS vs. genotype LL: OR=1.64, 95% CI=1.11-2.42, p=.01); however, this association was not observed in the cutoffs of the S allele >= 25.Conclusion: The results of this study indicate that there is a significant association between the HMOX1 (GT)(n) repeat length polymorphism and susceptibility to neonatal hyperbilirubinemia. Newborns carrying shorter (GT)(n) repeats in the HMOX1 gene promoter may have a higher risk of neonatal hyperbilirubinemia.