JAK2 46/1 haplotype is associated with <scp>JAK</scp>2 V617F – positive myeloproliferative neoplasms in Brazilian patients

Macedo, Luciana Conci; Santos, Bruna Cunha; Pagliarini-e-Silva, Sarah; Pagnano, Kátia Bórgia Barbosa; Rodrigues, Camila; Quintero, Fabiola; Ferreira, E.; Baraldi, Elaine Cristina; Ambrosio‐Albuquerque, Eliane Papa; Sell, Ana Maria; Visentainer, Jeane Eliete Laguila

doi:10.1111/ijlh.12380

Cited by 14 publications

(14 citation statements)

References 22 publications

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“…The significant associations between SNPs closest to these two lncRNAs and partial HP indicated that SNPs nearby PRANCR and TNK2–AS1 could be regarded as potential molecular markers affecting the immunity of dairy cows. In other studies, the association between SNPs and HP is also widely investigated [ 57 , 58 ], but the causal mutation within these two lncRNAs should be further explored for future animal breeding.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome sequencing analysis for the identification of stable lncRNAs associated with bovine Staphylococcus aureus mastitis

Tang

Dari

et al. 2021

J Animal Sci Biotechnol

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Background Staphylococcus aureus (S. aureus) mastitis is one of the most difficult diseases to treat in lactating dairy cows worldwide. S. aureus with different lineages leads to different host immune responses. Long non-coding RNAs (lncRNAs) are reported to be widely involved in the progress of inflammation. However, no research has identified stable lncRNAs among different S. aureus strain infections. In addition, folic acid (FA) can effectively reduce inflammation, and whether the inflammatory response caused by S. aureus can be reduced by FA remains to be explored. Methods lncRNA transcripts were identified from Holstein mammary gland tissues infected with different concentrations of S. aureus (in vivo) and mammary alveolar cells (Mac-T cells, in vitro) challenged with different S. aureus strains. Differentially expressed (DE) lncRNAs were evaluated, and stable DE lncRNAs were identified in vivo and in vitro. On the basis of the gene sequence conservation and function conservation across species, key lncRNAs with the function of potentially immune regulation were retained for further analysis. The function of FA on inflammation induced by S. aureus challenge was also investigated. Then, the association analysis between these keys lncRNA transcripts and hematological parameters (HPs) was carried out. Lastly, the knockdown and overexpression of the important lncRNA were performed to validate the gene function on the regulation of cell immune response. Results Linear regression analysis showed a significant correlation between the expression levels of lncRNA shared by mammary tissue and Mac-T cells (P < 0.001, R2 = 0.3517). lncRNAs PRANCR and TNK2–AS1 could be regarded as stable markers associated with bovine S. aureus mastitis. Several HPs could be influenced by SNPs around lncRNAs PRANCR and TNK2–AS1. The results of gene function validation showed PRANCR regulates the mRNA expression of SELPLG and ITGB2 within the S. aureus infection pathway and the Mac-T cells apoptosis. In addition, FA regulated the expression change of DE lncRNA involved in toxin metabolism and inflammation to fight against S. aureus infection. Conclusions The remarkable association between SNPs around these two lncRNAs and partial HP indicates the potentially important role of PRANCR and TNK2–AS1 in immune regulation. Stable DE lncRNAs PRANCR and TNK2–AS1 can be regarded as potential targets for the prevention of bovine S. aureus mastitis. FA supplementation can reduce the negative effect of S. aureus challenge by regulating the expression of lncRNAs.

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Section: Discussionmentioning

confidence: 99%

Transcriptome sequencing analysis for the identification of stable lncRNAs associated with bovine Staphylococcus aureus mastitis

Tang

Dari

et al. 2021

J Animal Sci Biotechnol

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“…These differences are contained in sites of single-base genetic alterations called single nucleotide variants (SNVs), which contribute to interindividual and inheritable differences in complex phenotypes [ 74 , 75 ]. A group of genetic variations present on the same chromosome, which are not easily separable by recombination and therefore tend to be inherited together, is called a haplotype [ 76 ].…”

Section: 46/1 Haplotypementioning

confidence: 99%

“…rs10974944 was the first to be associated with the emergence of MPNs [ 98 ]. Studies carried out in Europe, Japan, China, North America, and Brazil have shown that the variant allele of rs10974944 (G) is more frequent in all MPN patients (especially those positive for JAK2V617F) than in the control population [ 68 , 76 , 89 , 98 , 99 , 100 ].…”

Section: 46/1 Haplotypementioning

confidence: 99%

“…On the other hand, the fertile soil hypothesis assumes that hematopoietic stem cells carrying 46/1 have a selective advantage when oncogenic variants occur [ 96 , 99 ]. Even with different propositions, one hypothesis does not cancel out the other and both can coexist in the genetic scenario of these neoplasms [ 76 ].…”

Section: Association Between the 46/1 Haplotype And The Jak2v617f Var...mentioning

confidence: 99%

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The Contribution of JAK2 46/1 Haplotype in the Predisposition to Myeloproliferative Neoplasms

Paes

Silva

Tarragô

et al. 2022

IJMS

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Haplotype 46/1 (GGCC) consists of a set of genetic variations distributed along chromosome 9p.24.1, which extend from the Janus Kinase 2 gene to Insulin like 4. Marked by four jointly inherited variants (rs3780367, rs10974944, rs12343867, and rs1159782), this haplotype has a strong association with the development of BCR-ABL1-negative myeloproliferative neoplasms (MPNs) because it precedes the acquisition of the JAK2V617F variant, a common genetic alteration in individuals with these hematological malignancies. It is also described as one of the factors that increases the risk of familial MPNs by more than five times, 46/1 is associated with events related to inflammatory dysregulation, splenomegaly, splanchnic vein thrombosis, Budd–Chiari syndrome, increases in RBC count, platelets, leukocytes, hematocrit, and hemoglobin, which are characteristic of MPNs, as well as other findings that are still being elucidated and which are of great interest for the etiopathological understanding of these hematological neoplasms. Considering these factors, the present review aims to describe the main findings and discussions involving the 46/1 haplotype, and highlights the molecular and immunological aspects and their relevance as a tool for clinical practice and investigation of familial cases.

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“…Several previous studies found that rs10974944 was associated with the development of V617F‐positive MPNs (Jones et al, 2009; Kilpivaara et al, 2009; Tanaka et al, 2013). This observation might be due to the linkage between the JAK2 46/1 and V617F as many studies had demonstrated that this haplotype was associated with V617F‐positive myeloproliferative neoplasms in Brazilian (Macedo et al, 2015), Romanian (Trifa et al, 2010), Japanese (Tanaka et al, 2013) and other populations (Anelli et al, 2018; Stolyar et al, 2018). However, the results of our study indicated that in the Vietnamese population, the linkage disequilibrium between rs10974944 and rs77375493 (V617F) was not tight, yet rs10974944 still had a strong association with MPNs, suggested that the effect of rs10974944 on MPNs phenotype was independent of V617F profile.…”

Section: Discussionmentioning

confidence: 99%

JAK2 rs10974944 is associated with both V617F‐positive and negative myeloproliferative neoplasms in a Vietnamese population: A potential genetic marker

Ngoc

Hau

Vuong

et al. 2022

Molec Gen & Gen Med

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The JAK2 gene encodes for a non‐receptor tyrosine kinase that plays a key role in the JAK/STAT signaling transfer pathway. Genetic polymorphisms of this gene have been indicated to be associated with myeloproliferative neoplasm‐associated thrombosis in recent studies. This research aimed to evaluate the association between the variant rs10974944 and different types of Myeloproliferative neoplasms disorders in the Vietnamese population. DNA samples were obtained from 172 essential thrombocythemia patients, 14 primary myelofibrosis patients, 76 polycythemia vera patients, and 192 healthy controls. The JAK2 rs10974944 and V617F genotypes were identified by the polymerase chain reaction‐restriction fragment length polymorphism genotyping and Sanger sequencing methods. Results showed that there was a strong association between rs10974944 and Myeloproliferative neoplasms phenotype (p < .0001) and the most significant association was observed in the recessive model of the mutant allele (G). The G allele carriers had a 1.74, 2.86, and 3.03 higher risk of getting essential thrombocythemia, primary myelofibrosis, and polycythemia vera, respectively. Interestingly, this effect of rs10974944 seemed to be independent of the JAK2 V617F genotype. The distribution of rs10974944 genotypes were significantly different between V617F‐positive and negative groups (p = .008). Moreover, the GG genotype of rs10974944 was observed to be associated with the risk of getting Myeloproliferative neoplasms both in JAK2 V617F‐positive group, and for the first time in JAK2 V617F‐negative patients. A systematic meta‐analysis in different populations strengthened the evidence regarding the correlation between rs10974944 and myeloproliferative neoplasm disorders. To sum up, our results suggested that rs10974944 can be used as a predisposition screening marker for predicting Myeloproliferative neoplasms susceptibility.

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JAK2 46/1 haplotype is associated with JAK2 V617F – positive myeloproliferative neoplasms in Brazilian patients

Abstract: In agreement with previous reports, JAK2 46/1 haplotype for JAK2 V617F was associated with cMPN positive in Brazilian patients.

Cited by 14 publications

References 22 publications

Transcriptome sequencing analysis for the identification of stable lncRNAs associated with bovine Staphylococcus aureus mastitis

Transcriptome sequencing analysis for the identification of stable lncRNAs associated with bovine Staphylococcus aureus mastitis

The Contribution of JAK2 46/1 Haplotype in the Predisposition to Myeloproliferative Neoplasms

JAK2 rs10974944 is associated with both V617F‐positive and negative myeloproliferative neoplasms in a Vietnamese population: A potential genetic marker

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