Lack of association between 14-3-3 beta gene (YWHAB) polymorphisms and sporadic Creutzfeldt-Jakob disease (CJD)

Abstract

14-3-3 proteins are highly abundant in brain tissue. The presence of 14-3-3 at elevated levels in the cerebrospinal fluid has been considered as a biomarker for sporadic Creutzfeldt-Jakob disease (CJD). Recent studies showed that 14-3-3 beta protein interacts with the N-terminal amino acids 1-38 and with the central hydrophobic amino acids 106-126 of prion protein. This interaction may indicate a role of 14-3-3 beta in the biological function of PrP and in the pathogenesis of prion disease. An association between the polymorphisms of 14-3-3 beta gene (YWHAB) and prion disease has not been reported previously. In order to investigate whether YWHAB polymorphisms are associated with sporadic CJD in the Korean population, we compared genotype distribution and allele frequencies of six YWHAB polymorphisms in 244 sporadic CJD patients and 219 healthy Koreans. Of six polymorphisms identified, four single nucleotide polymorphisms (SNPs) were known previously (c.60A>C, c.685-120G>A, c.685-89G>A, 92G>A) and two SNPs were novel (c.185T>A and c.377A>C). Two novel polymorphisms were identified within 3'-untranslated region of exon 6. We could not find significant differences in genotype and allele frequencies of the six YWHAB polymorphisms between the controls and sporadic CJD patients. These results indicate that these six YWHAB polymorphisms are not associated with the genetic susceptibility to sporadic CJD. This is the first genetic association study of YWHAB in sporadic CJD.