Book Chapter
Genotypes of sickle cell disease
Fecha
2015Autor
FAVELA-MENDOZA, A.F.
MARTINEZ-CORTES, G.
HERNANDEZ-ZARAGOZA, M.
SALAZAR-FLORES, J.
MUNOZ-VALLE, J.F.
MARTINEZ-SEVILla, V.M.
VELAZQUEZ-SUAREZ, N.Y.
RANGEL-VILLALOBOS, H.
Institución
Resumen
CYP2C19 is a polymorphic enzyme that metabolizes a wide variety of therapeutic drugs that has been associated with altered enzymatic activity and adverse drug reactions. Differences in allele frequencies of the CYP2C19 gene have been detected in populations worldwide. Thus, we analysed the alleles CYP2C19*2, CYP2C19*3, CYP2C19*4 and CYP2C19*5 related to the poor metabolizer (PM) phenotype in a Mexican population sample (n = 238), as well as CYP2C19*17, unique allele related to ultrarapid metabolizer phenotype (UMs). Genotypes were determined using SNaPshot and TaqMan qPCR assays. In addition to the wild-type CYP2C19*1 allele (77.1%), we only found CYP2C19*17 (14.3%) and CYP2C19*2 (8.6%). Comparison with previous population reports demonstrated that these two SNPs are homogeneously distributed in Latin America (P>0.05). Based on comparison with a previous pharmacokinetic study that determined the frequency of CYP2C19 phenotypes in the same population (western Mexican), we obtained the following findings: (i) based on the difference between the frequency of genotypes CYP2C19*2/*2 (presumably PM) versus the observed prevalence of PM phenotypes (0.4 versus 6.3%; ?2=9.58, P = 0.00196), we inferred the plausible presence of novel CYP2C19 alleles related to the PM phenotype; (ii) the prevalence of UMs was in disagreement with the dominant inheritance pattern suggested for CYP2C19*17 (23.1 versus 4%; P<0.00001); (iii) the apparent recessive inheritance pattern of CYP2C19*17, based on the agreement between homozygous CYP2C19*17/*17 (presumably UMs) and the observed prevalence of UMs (2.1 versus 4%; (?2=1.048; P = 0.306). " 2015 Indian Academy of Sciences",,,,,,"10.1007/s12041-015-0477-1",,,"http://hdl.handle.net/20.500.12104/41716","http://www.scopus.com/inward/record.url?eid=2-s2.0-84923261662&partnerID=40&md5=609b3d0e44d0e37b92420aa5676bfb10 http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=25846871",,,,,,,,"Journal of Genetics",,,,,,"Scopus MEDLINE WOS",,,,,,"allele CYP2C19*17.; CYP2C19; Mexican population; poor metabolizer; ultrarapid metabolizer",,,,,,"Genetic variability of CYP2C19 in a Mexican population: contribution to the knowledge of the inheritance pattern of CYP2C19*17 to develop the ultrarapid metabolizer phenotype",,"Article in Press"
"43515","123456789/35008",,"Perea-Díaz, F.J., División de Genética, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, Mexico; Ibarra-Cortés, B., Instituto de Genética Humana Dr Enrique Corona Rivera, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico",,"Perea-Diaz, F.J. Ibarra-Cortes, B.",,"2013",,"In this chapter, we will discuss the genotypes and phenotypes associated with the sickle syndromes. There are four major genotypes for sickle diseases, including sickle cell trait, sickle cell anemia, and compound sickle-cell-beta-thalassemia and sickle cell-abnormal hemoglobin variants. We mention the main clinical complications observed in different genotypes as a way to emphasize the phenotypic variability of sickle syndromes. We also briefly discuss the tracing of HbS mutations by haplotype and its use as a predictor of clinical severity. We will describe HbF and some genes involved in regulating its expression, all which are considered modulators of clinical severity in patients with sickle cell diseases. Finally, we will discuss the effect of alpha-thalassemia in some clinical complications associated with sickle cell diseases. " 2013 by Nova Science Publishers, Inc. All rights reserved.