CBS and PAI-1 Polymorphisms as Modulators of Clinical Severity Profile in Sickle Cell Disease

The Sickle Cell Disease (SCD) causes in the patients accentuated hemolysis, impaired vaso-activity and the clinical severity is variable. Genetics factors can be modulate the SCD pathophysiology, such as coagulation-related polymorphisms. In the present study, we investigated the cystathionine beta-synthase polymorphism (CBS - 844ins68) and the 4G/5G plasminogen-activator inhibitor type I polymorphism (-675pb, PAI1) in SCD patients, in order to verify if these genetic factors, along with SCD genotypes, influence the clinical severity profile. The study group was constituted by 462 SCD patients from the HEMORIO, with age among 5 at 65 years-old (median of 20 years-old), being 249 female and 213 male. All the patients were diagnosed for hemoglobinopathies and the PCR-RFLP used to SCD genotype confirmation. The 844ins68 polymorphism of the CBS was investigated by PCR, and the 4G/5G of the PAI1 by PCR-RFLP (restriction enzyme BselI). To clinical severity classification we used the online program “Sickle Cell Disease Severity Calculator”. The statistics analyses were performed by STATISTICA 8.0 through chi-square test and the General Linear Models (GLM) follow Fisher post-hoc test. Our results showed interaction of SCA and CBS polymorphism, and the severity score was higher in the patients with SS with Ins-/Ins- genotype (0.50 ± 0.22) and SS with Ins-/Ins+ genotype (0.47 ± 0.22). But, by knowing the SS genotype that confere clinical severe in SCD patient, we suggest that the SCD clinical severity is modulated mainly by the disease genotype, being the SS with a higher severity score, independent of investigated polymorphisms.

Author(s): Okumura JV*, Junior EB, Humberto da Silva DG, Lidiane de Souza Torres, Salvarani M, Patrícia Pereira do Nascimento, Sybuia LS, Chaves NA, Lobo CCL and Bonini-Domingos CR

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