Haptoglobin Genotypes in Sickle-Cell Disease

Abstract

We compared the frequencies of the haptoglobin (Hp) genotypes of 775 Brazilian patients with sickle-cell disease divided into the following age groups: 3 months-5 years, 6-10 years, 11-15 years, 16-20 years, and over 20 years. The last group (>20 years) was also compared with a healthy control group and was further divided into subgroups including only subjects aged 21-30 years (V.a and Control.a) and over 30 years (V.b and Control.b). There was no significant difference in the frequencies of the Hp genotypes between the different patient groups or between the patients and controls. However, the Hp2-2 genotype was always less frequent than the Hp1-1 genotype in the patient groups, whereas the opposite was observed in healthy controls. The frequency of Hp2-2 was 25.0% in patients in the 21-30 years age group and fell to 19.5% in those over 30 years. In the controls, the corresponding frequency was around 28%. Although our results do not allow us to conclude that Hp genotypes on their own confer greater or lesser selective advantage on sickle-cell disease patients in the population studied, this polymorphism may, when combined with other genetic and environmental factors, contribute to the clinical diversity observed in this disease.

Haptoglobin gene polymorphisms and interleukin-6 and -8 levels in patients with sickle cell anemia

“…Hp has emerged as one of the most important SCD phenotypic modulators, as it is a protein with high capability to bind to free Hb in the plasma, forming the Hp–Hb complex and thereby preventing heme-catalyzed oxidative damage. 32 Although the three Hp phenotypes have the same ability to bind to free Hb, the speed of heme release can be related to differences in their molecular size. Hp 2-2 , which is a more complex polypeptide, removes iron more slowly to the extravascular space thereby allowing free Hb to be in the circulation for a longer period, causing more oxidative stress.…”

“…This pattern agrees with most studies on the distribution of haplotype polymorphisms in SCD. 32 , 34 …”

“…There have been inconsistencies in the distribution of Hp genotypes in the SCA population. In 2011, Santos et al 32 reported that the Hp 2-2 phenotype in Brazilian SCA patients was less frequent than the Hp 1-1 phenotype and hypothesized that Hp 2-2 might be associated with worse prognosis because of lower antioxidant capacity and higher inflammatory response. In the current study, the Hp 1-1 phenotype was less common (16.7%), which agrees with the findings of Adekile & Haider in Kuwaiti patients with SCD in which only 4.9% had Hp 1-1 compared to 52.4% in those with the Hp 2-2 genotype.…”

Haptoglobin: an emerging candidate for phenotypic modulation of sickle cell anemia?

“…The Hp2-2 genotype was found to be less represented in SCD patients in Nigeria ( n = 54) 16 and in SCA patients in the northeast of Brazil ( n = 599). 17 On the other hand, the Hp1-1 genotype was less represented in SCD patients from Kuwait ( n = 82) 16 and in SCA patients from the southeast of Brazil ( n = 60). 15 This disagreement may reflect the genetic background of the patients as well as the influence of environmental factors and, especially, the sample size, characteristics and quality in each study.…”

Sickle cell disease: chest and abdominal manifestation-A CT based study

“…Also, other heterozygous types of Hb S may form due to combination with another different abnormal gene, such as sickle-hemoglobin C disease (Hb SC) or Hb S-beta thalassemia (Hb S-tha). [6] In Hb SS patients, severe anemia is caused by excessive destruction of the red cells. The bone marrow rate of hematopoiesis is significantly increased, but does not match the rate of destruction.…”