The Role of Caspase Genes Polymorphisms in Genetic Susceptibility to Philadelphia-Negative Myeloproliferative Neoplasms in a Portuguese Population

Abstract

Our main aim was to evaluate the role of caspases' genes SNPs in Philadelphia-chromosome negative chronic myeloproliferative neoplasms (PN-MPNs) susceptibility. A case-control study in 133 Caucasian Portuguese PN-MPNs patients and 281 matched controls was carried out, studying SNPs in apoptosis related caspases: rs1045485 and rs1035142 (CASP8), rs1052576, rs2308950, rs1132312 and rs1052571 (CASP9), rs2227309 and rs2227310 (CASP7) and rs13006529 (CASP10). After stratification by pathology diagnosis for essential thrombocythemia (ET), female gender or JAK2 positive, there is a significant increased risk for those carrying at least one variant allele for CASP9 (C653T) polymorphism (OR 2.300 CI 95% [1.180-4.484], P = 0.014). However, when considered individually, none of the studied caspases polymorphisms was associated with PN-MPNs risk. Our results do not reveal a significant involvement of caspase genes polymorphisms on the individual susceptibility towards PN-MPNs as a whole. However, for essential thrombocythemia (ET), female gender or JAK2 positive, there is a significant increased risk to those carrying at least one variant allele for CASP9. Although larger studies are required to confirm these results and to provide conclusive evidence of association between these and other caspases variants and PN-MPNs susceptibility, these new data may contribute to a best knowledge of the pathophysiology of these disorders and, in the future, to a more rational and efficient choice of therapeutic strategies to be adopted in PN-MPNs treatment.

Effects of polymorphic DNA genes involved in BER and caspase pathways on the clinical outcome of myeloproliferative neoplasms under treatment with hydroxyurea

“…The characteristics of each SNP under study were previously described and published (16,41,42), while the genotype frequencies and therapeutic distribution determined according to survival are shown in Table II.…”

Genetic polymorphisms associated with telomere length and risk of developing myeloproliferative neoplasms

“…Moreover, there are several evidences for a causative role of somatic mutations in MPN development, such as the V617F mutation in the JAK2 gene and mutations in CALR and MPL 6,7 . In addition, common low penetrance variants have been associated with the disease risk, in particular, seven single nucleotide polymorphisms (SNPs) have been identified through three genome-wide association studies (GWAS) 6,8,9 and, through case-control studies, additional hits such as the 46/1 JAK2 haplotype 10 and several SNPs belonging to genes involved in DNA repair, apoptosis, inflammation, and detoxification [11][12][13][14][15][16] .…”

Research and application of hydrostatic high pressure in tumor vaccines (Review)

“…In addition, specific antibody blockade of calreticulin or depletion of caspase-2 significantly inhibited DC phagocytosis (119). While it remained unclear how caspase-2 regulated the exposure of calreticulin, the localization of this caspase in the ER and Golgi systems suggested the possible involvement in regulating the transit mechanisms (124). However, inhibition of ROS production was not sufficient to eliminate HHP-induced calreticulin exposure, suggesting that ROS-independent mechanisms may also be involved in this process.…”