分子遺伝医学

Association of Heme Oxygenase-1 (Number of GT Repeats) with The Methemoglobin Levels in Recessive Congenital Methemoglobinemia in Indian Population

Abstract

Das S, Chiddarwar A, Warang P and Kedar P

Heme oxygenase-1 (HO-1) is important in the defense against oxidative stress. Length polymorphisms in this GT repeat region correlate with levels of HO-1 expression and associates with several diseases. The aim of this study was to test for possible association of HO-1 (number of GT repeats) with methemoglobin levels in recessive congenital methemoglobinemia in Indian population. Genotyping of DNA isolated from whole blood of 25 RCM patients due to NADH cytochrome b5 reductase deficiency and 50 healthy controls was performed. Fragment size analysis by sequencing was used for genotype/allele definition by ABI 3130 genetic analyzer and size of PCR product was determined by Gene Mapper software. Significance of findings was tested using χ(2) test. The HO-1 (number of GT repeats) polymorphisms was significantly associated with RCM. Results of genotyping analysis indicated that a genotype carrying short alleles (<24 (GT)n repeats was preferentially associated with RCM patients than in control (P<0.001). The short allele (<24 GT repeats) genotype were present in 82% of the methemoglobinemia patients group and long allele (≥31 GT repeats) observed in the normal control group. This study is supporting the association of HO-1 (number of GT repeats) polymorphism and RCM. . Allele and genotype frequencies for HO-1 polymorphisms show significant association with disease severity. This data could also be valuable to the clinicians, mainly hematologists, when attempting a definitive diagnosis for the cause of methemoglobinemia that will help clinical decisions for treatment.