Haptoglobin genotypes in sickle cell disease / Genotipos da haptoglobina nas doenças falciformes
AUTOR(ES)
Magnun Nueldo Nunes dos Santos
DATA DE PUBLICAÇÃO
2009
RESUMO
Oxidative stress, particularly in the endothelium, exerts a strong influence on the genesis of sickle cell disease (SCD) vasoocclusion and, consequently, on patients clinical evolution and survival. The pathophysiology of SCD is centered on the polymerization property of the desoxy-hemoglobin (Hb) S, but genetic factors can act as modulators of its clinical complications. Haptoglobin (Hp) is a plasma glycoprotein whose primary function is to bind to free hemoglobin, preventing excretion of iron by the kidneys and protecting blood vessels from its oxidative effects. It is also an acute phase positive protein with immunomodulatory capacity. Two codominant alleles, HP1 and HP2, result in 3 main genotypes / phenotypes, Hp1-1, Hp2-1 and Hp2-2, which correspond to proteins with different functional characteristics. Recently, it has been suggested that the Hp2-2 genotype frequency reduces with age in SCD patients and that this reduction may be associated with a worse prognosis. In vitro experiments have shown lower antioxidant capacity and higher inflammatory reactivity related to the phenotype (Hp2-2). Thus, the aim of this study was to determine, by allele-specific PCR, the Hp genotypes in 775 patients with SCD (599 HbSS, 94 HbSC, 81 HbS/ß-thalassemia and 1 HbS/ HbDeer Lodge), followed at HEMOPE (Pernambuco Blood Center, in the northeast region of Brazil), divided into 5 different age groups (3 months - 5 years - n=237, 6-10 years - n=96, 11-15 years - n=89, 16-20 years - n=95 and >20 years - n=258). Those over 20 years of age were also compared with healthy controls (n=236, blood donors in the same country region, adjusted for the ratio between the gender and matched with patients by age and predominant ethnic characteristics); both groups were subdivided into 2 different age groups: 21 to 30 years (140 patients and 111 controls) and more than 30 years-old (118 patients and 125 controls). The distributions of Hp genotypic frequencies did not differ significantly among the five main groups of patients (p=0.7908), even when they, additionally, were divided into age groups from 3 months to 16 years (pediatric group - n= 447) and more than 16 years (adult group - n = 328) (p=0.7421). When the patients were compared to the control group, the frequencies of genotype Hp2-2 were lower (22.06% in means of five groups of patients - or 22.48% of group V versus 28.39% in controls); in patients over 20 years, this genotype was reduced with increased age, while it remained stable in controls (as seen from the comparison of the subgroups from 21 to 30 years of age - 25% of Hp2-2 in patients versus 28,83% in controls, and more than 30 years-old - 19.49% of Hp2-2 in patients versus 28% in controls). These differences, however, were not statistically significant (p = 0.6479 and 0.3780, respectively). Our results indicate a reduction in Hp2-2 genotype frequencies of patients, compared to the healthy controls, intensified with the progression of age from adulthood, but also suggest that the consequences resulting from their presence in vivo are probably minimized by compensatory mechanisms inherent in complex organisms. The population analyzed here was very expressive, but was not ideal to be considered as representative of SCD patients as a whole yet. These results apply only to the group of patients studied here. Other comparisons performed in search of the existence of interaction among the Hp polymorphism and Hb Fetal levels, a-thalassemia and cluster ß haplotypes also revealed no significant differences
ASSUNTO(S)
hemoglobina polymorphism (genetic) polimorfismo (genetica) haptoglobinas hemoglobin sickle cell disease anemia falciforme haptoglobins
