Sickle Cell Anemia Patients in Use of Hydroxyurea: Association between Polymorphisms in Genes Encoding Metabolizing Drug Enzymes and Laboratory Parameters

Abstract

This study investigated associations between SNPs in genes encoding metabolizing drug enzymes and laboratory parameters in sickle cell anemia patients under hydroxyurea (SCA-HU + ). We evaluated hematologic and biochemical parameters by electronic methods and SNPs by PCR-RFLP and multiplex PCR in 35 SCA-HU + patients and 67 SCA-HU − patients. The HbS, total cholesterol, lactate dehydrogenase, aspartate aminotransferase, total bilirubin and fractions levels, and leukocyte, eosinophil, monocyte, and erythroblast counts were reduced in SCA-HU + patients (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mi>p</mml:mi><mml:mo>&lt;</mml:mo><mml:mn>0.05</mml:mn></mml:math>). Moreover, they presented higher HbF, C-reactive protein, and ferritin levels and elevated MCH and MCV values (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mi>p</mml:mi><mml:mo>&lt;</mml:mo><mml:mn>0.05</mml:mn></mml:math>). Genotype frequencies of variants GA + AA of MPO −463G&gt;A and c1c2 + c2c2 of CYP2E1 −1293G&gt;C/−1053C&gt;T were higher in SCA-HU + patients (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"><mml:mi>p</mml:mi><mml:mo>&lt;</mml:mo><mml:mn>0.05</mml:mn></mml:math>). Independent associations were found between the variant A allele and lower total cholesterol, between c2 allele and low alpha-1 antitrypsin and between the null GSTT1 variant and high indirect and total bilirubin in SCA-HU + patients. In SCA-HU − patients, independent associations were found between the variant A allele and high uric acid and between c2 allele and high urea. Our results suggest that SNPs MPO −463G&gt;A, CYP2E1 −1293G&gt;C/−1053C&gt;T, and GSTT1 can be associated with alterations in lipid, inflammatory, renal, hemolytic, and hepatic profiles. However, further studies are needed to elucidate these associations.