BACKGROUND: Heme oxygenase (HO) is the initial, rate-limiting enzyme in the conversion of heme to bilirubin. Dinucleotide (GT)n repeat length in the promoter region of the encoding gene modulates transcription: shorter alleles, in contrast with longer allele counterparts, are associated with greater gene expression and should result in increased heme catabolism. OBJECTIVE: We compared the rates of heme catabolism and plasma total bilirubin (TB) between HO-1 promoter genotypes of varying (GT)n repeat lengths in glucose-6-phosphate dehydrogenase (G6PD)-normal and -deficient neonates. METHODS: HO-1 promoter length was determined from genomic DNA from previous studies by size discrimination of fluorescently-labeled PCR products with capillary electrophoresis. Sizing was confirmed by sequencing homozygote samples. Alleles were categorized as: short (≤24 GT repeats), medium (25-33 GT repeats), and long (≥34 GT repeats). Previously determined values for blood carboxyhemoglobin, corrected for inspired carbon monoxide (COHbc), and TB were used to determine the rate of heme catabolism and 3rd day TB values for each HO-1 promoter length genotype, respectively. G6PD Mediterranean was determined by PCR analysis. RESULTS: Neither COHbc nor TB values were significantly different between various HO-1 promoter genotypes for either G6PD-normal or -deficient neonates. CONCLUSIONS: In the steady state, HO-1 promoter genotypes, based on the length of (GT)n repeats, do not modulate heme catabolism or 3rd day TB values in either G6PD-normal or -deficient neonates.
BACKGROUND:Heme oxygenase (HO) is the initial, rate-limiting enzyme in the conversion of heme to bilirubin. Dinucleotide (GT)n repeat length in the promoter region of the encoding gene modulates transcription: shorter alleles, in contrast with longer allele counterparts, are associated with greater gene expression and should result in increased heme catabolism. OBJECTIVE: We compared the rates of heme catabolism and plasma total bilirubin (TB) between HO-1 promoter genotypes of varying (GT)n repeat lengths in glucose-6-phosphate dehydrogenase (G6PD)-normal and -deficient neonates. METHODS: HO-1 promoter length was determined from genomic DNA from previous studies by size discrimination of fluorescently-labeled PCR products with capillary electrophoresis. Sizing was confirmed by sequencing homozygote samples. Alleles were categorized as: short (≤24 GT repeats), medium (25-33 GT repeats), and long (≥34 GT repeats). Previously determined values for blood carboxyhemoglobin, corrected for inspired carbon monoxide (COHbc), and TB were used to determine the rate of heme catabolism and 3rd day TB values for each HO-1 promoter length genotype, respectively. G6PD Mediterranean was determined by PCR analysis. RESULTS: Neither COHbc nor TB values were significantly different between various HO-1 promoter genotypes for either G6PD-normal or -deficient neonates. CONCLUSIONS: In the steady state, HO-1 promoter genotypes, based on the length of (GT)n repeats, do not modulate heme catabolism or 3rd day TB values in either G6PD-normal or -deficient neonates.
Authors: Ruka Nakasone; Mariko Ashina; Shinya Abe; Kenji Tanimura; Hans Van Rostenberghe; Kazumichi Fujioka Journal: Int J Environ Res Public Health Date: 2021-03-29 Impact factor: 3.390