Genótipos da talassemia alfa e haplótipos do agrupamento de genes da globina beta como moduladores de gravidade na Doença falciforme em crianças do Programa Estadual de Triagem Neonatal de Minas Gerais matriculados no Hmeocentro de Belo Horizonte da Fundação Hemominas

Abstract

Objectives: To examine associations between the alpha-thalassemia (-Thal) genotypes and the S gene cluster haplotypes (S haplotypes) with clinical and hematological features in a population of children derived from the Newborn Screening Program of Minas Gerais (NSPMG) and followed-up at the Blood Center of Belo Horizonte (HBH) of HEMOMINAS Foundation. Methods: children with electrophoretic profile compatible with sickle cell anemia (SS or S0-thalassemia) screened by NSP-MG between 01/01/1999 to 12/31/2006 and followed-up at HBH were included in a randomized retrospective cohort study. Data were collected from patients medical records at HBH. All patients were followed-up for a minimum of two years and a half, up to 6/30/2009. Genotyping of -Thal was performed by multiplex PCR (alleles: -3.7; -4.2; --SEA; --FIL; --MED; -()20.5 e --THAI). S haplotypes were determined by PCR-RFLP. Results: 221 children were analyzed, 119 (53.8%) females and 102 (46.2%) males. The age ranged from 2.5 to 10.4 years. Two hundred and eight (94.1%) were homozygous for the S allele and 13 (5,9%) were S0-thal. Of the 208 SS subjects, 58 (27.9%) were heterozygous (-3.7/) and three (1.4%) homozygous for -Thal (-3.7/-3.7). Of the 13 S0-thal subjects, five (38.5%) were heterozygous (-3.7/). Among the 208 SS subjects, 82 (39.43%) were CAR/CAR, 69 (33.17%) Ben/CAR, 49 (23.56%) Ben/Ben, two (0.96%) CAR/Atp, two (0.96%) Ben/Atp, two (0.96%) Arab-Indian/Ben and two (0.96%) could not be genotyped. Of 412 S chromosomes genotyped in homozygous subjects for S hemoglobin (SS), 57% were CAR type, 41.5% were Ben, 0.5% were Arab-Indian e 1% were atypical. In homozygous subjects for S hemoglobin, the presence of -Thal was significantly associated with decreased levels of MCV, MCH, WBC and reticulocytes, and not with the levels of total Hb, Hb F and platelets. There was no significant association between S haplotypes and total Hb, Hb F, MCV, MCH, WBC and reticulocyte levels. Platelet count was significantly higher in the group with Ben/CAR genotype when compared with the Ben/Ben and CAR/CAR. There was no significant association between the presence of -Thal and the frequency of episodes of acute chest syndrome, blood transfusions and acute splenic sequestration. The presence of -Thal was strongly associated with decreased risk of cerebrovascular disease (abnormal transcranial Doppler or clinical stroke; P=0.007). There was no significant association between S haplotypes and the frequency of episodes of acute xiv chest syndrome, blood transfusions, acute splenic sequestration and cerebrovascular disease. Conclusions: The most important significant association found was between co-inheritance of -Thal and decreased risk of cerebrovascular disease. Neither the presence/absence of - Thal nor S haplotypes can alone predict the clinical course of the disease. Other modulating factors should be investigated to subphenotype the disease and thus be used together as a clinical tool in monitoring patients. It should be noted that the sample of children has come from a single source and was randomized; follow-up was uniform and done in a single blood center, what reinforces the conclusions of the study.