RESUMO
INTRODUCTION: The Hb Deer Lodge (ß2 His>Arg; HBB:c.8A>G) is a structural hemoglobin variant described in some populations around the world, characterized by increased oxygen affinity, but does not confer clinical symptoms to its carriers. The coinheritance of the Hb Deer Lodge with the most common hemoglobin variant, Hb S, has been reported only once; however, functional data were not described. Here we show a case of the Hb S and Hb Deer Lodge carrier in heterozygosity. METHODS: The Hb S and Hb Deer Lodge association was identified by High-Performance Liquid Chromatography (HPLC), reverse phase HPLC and the ß globin gene sequencing. The functional characterization of this interaction was obtained using the O2 dissociation curve, determination of the cooperativity between the globin chains and the Bohr effect in the presence and absence of organic phosphates. RESULTS: When the Hb S and Hb Deer Lodge were associated, there was a decrease in cooperativity, no significant changes in oxygen affinity and no significant Bohr effect changes. CONCLUSION: Despite these genetic variations, the carrier showed no hematological alterations and no clinical symptoms, possibly due to the high oxygen affinity of the Hb Deer Lodge, which interferes with the Hb S polymerization.
RESUMO
Hyperbilirubinemia in patients with sickle cell anemia (SCA) as a result of enhanced erythrocyte destruction, lead to cholelithiasis development in a subset of patients. Evidence suggests that hyperbilirubinemia may be related to genetic variations, such as the UGT1A1 gene promoter polymorphism, which causes Gilbert syndrome (GS). Here, we aimed to determine the frequencies of UGT1A1 promoter alleles, alpha thalassemia, and ßS haplotypes and analyze their association with cholelithiasis and bilirubin levels. The UGT1A1 alleles, -3.7 kb alpha thalassemia deletion and ßS haplotypes were determined using DNA sequencing and PCR-based assays in 913 patients with SCA. The mean of total and unconjugated bilirubin and the frequency of cholelithiasis in GS patients were higher when compared to those without this condition, regardless of age (P < 0.05). Cumulative analysis demonstrated an early age-at-onset for cholelithiasis in GS genotypes (P < 0.05). Low fetal hemoglobin (HbF) levels and normal alpha thalassemia genotype were related to cholelithiasis development (P > 0.05). However, not cholelithiasis but total and unconjugated bilirubin levels were associated with ßS haplotype. These findings confirm in a large cohort that the UGT1A1 polymorphism influences cholelithiasis and hyperbilirubinemia in SCA. HbF and alpha thalassemia also appear as modulators for cholelithiasis risk.