The JAK2 46/1 haplotype in splanchnic vein thrombosis

Kouroupi, Eirini; Kiladjian, Jean‐Jacques; Chomienne, Christine; Dosquet, Christine; Bellucci, Sylvia; Valla, Dominique; Cassinat, Bruno

doi:10.1182/blood-2011-03-343657

Cited by 13 publications

(7 citation statements)

References 11 publications

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“…We found that JAK2 polymorphism was not associated with BCS susceptibility. Our observations were at variance with those reported by some researchers [ 19 , 28 ], who found that 46/1 haplotype is present more frequently in BCS patients. However, the significant difference disappeared when including portal vein thrombosis (PVT) patients.…”

Section: Discussioncontrasting

confidence: 99%

Association between JAK2 rs4495487 Polymorphism and Risk of Budd-Chiari Syndrome in China

Zhang

et al. 2015

Gastroenterology Research and Practice

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Myeloproliferative neoplasms (MPNs) are the leading cause of Budd-Chiari syndrome (BCS), and the C allele of JAK2 rs4495487 was reported to be an additional candidate locus that contributed to MPNs. In the present study, we examined the role of JAK2 rs4495487 in the etiology and clinical presentation of Chinese BCS patients. 300 primary BCS patients and 311 healthy controls were enrolled to evaluate the association between JAK2 rs4495487 polymorphism and risk of BCS. All subjects were detected for JAK2 rs4495487 by real-time PCR. Results. The JAK2 rs4495487 polymorphism was associated with JAK2 V617F-positive BCS patients compared with controls (P < 0.01). The CC genotype increased the risk of BCS in patients with JAK2 V617F mutation compared with individuals presenting TT genotype (OR = 13.60, 95% CI = 2.04–90.79) and non-CC genotype (OR = 12.00, 95% CI = 2.07–69.52). We also observed a significantly elevated risk of combined-type BCS associated with CC genotype in the recessive model (OR = 4.44, 95% CI = 1.31–15.12). This study provides statistical evidence that the JAK2 rs4495487 polymorphism is susceptibility factor JAK2 V617F positive BCS and combined BCS in China. Further larger studies are required to confirm these findings.

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Section: Discussioncontrasting

confidence: 99%

Association between JAK2 rs4495487 Polymorphism and Risk of Budd-Chiari Syndrome in China

Zhang

et al. 2015

Gastroenterology Research and Practice

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“…Smalberg et al [19] recently demonstrated that the 46/1 haplotype is associated with the development of JAK2 V617F-positive splenic vein thrombosis (SVT), but the existence of JAK2 V617F-negative SVT patients also indicates an important role for the 46/1 haplotype in the etiology and diagnosis of SVT-related MPNs. In contrast, Kouroupi et al [20] showed that the 46/1 haplotype is not a susceptibility locus for the development of SVT. Thus, further exploration is required to clarify whether the JAK2 germline variation is a risk factor of thrombosis.…”

Section: Discussionmentioning

confidence: 98%

The C allele of JAK2 rs4495487 is an additional candidate locus that contributes to myeloproliferative neoplasm predisposition in the Japanese population

et al. 2012

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BackgroundPolycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) are myeloproliferative neoplasms (MPNs) characterized in most cases by a unique somatic mutation, JAK2 V617F. Recent studies revealed that JAK2 V617F occurs more frequently in a specific JAK2 haplotype, named JAK2 46/1 or GGCC haplotype, which is tagged by rs10974944 (C/G) and/or rs12343867 (T/C). This study examined the impact of single nucleotide polymorphisms (SNPs) of the JAK2 locus on MPNs in a Japanese population.MethodsWe sequenced 24 JAK2 SNPs in Japanese patients with PV. We then genotyped 138 MPN patients (33 PV, 96 ET, and 9 PMF) with known JAK2 mutational status and 107 controls for a novel SNP, in addition to two SNPs known to be part of the 46/1 haplotype (rs10974944 and rs12343867). Associations with risk of MPN were estimated by odds ratios and their 95% confidence intervals using logistic regression.ResultsA novel locus, rs4495487 (T/C), with a mutated T allele was significantly associated with PV. Similar to rs10974944 and rs12343867, rs4495487 in the JAK2 locus is significantly associated with JAK2-positive MPN. Based on the results of SNP analysis of the three JAK2 locus, we defined the "GCC genotype" as having at least one minor allele in each SNP (G allele in rs10974944, C allele in rs4495487, and C allele in rs12343867). The GCC genotype was associated with increased risk of both JAK2 V617F-positive and JAK2 V617F-negative MPN. In ET patients, leukocyte count and hemoglobin were significantly associated with JAK2 V617F, rather than the GCC genotype. In contrast, none of the JAK2 V617F-negative ET patients without the GCC genotype had thrombosis, and splenomegaly was frequently seen in this subset of ET patients. PV patients without the GCC genotype were significantly associated with high platelet count.ConclusionsOur results indicate that the C allele of JAK2 rs4495487, in addition to the 46/1 haplotype, contributes significantly to the occurrence of JAK2 V617F-positive and JAK2 V617F-negative MPNs in the Japanese population. Because lack of the GCC genotype represents a distinct clinical-hematological subset of MPN, analyzing JAK2 SNPs and quantifying JAK2 V617F mutations will provide further insights into the molecular pathogenesis of MPN.

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“…Villani et al () replicated these findings – 46/1 haplotype was over‐represented in V617F + patients with SVT but not in the JAK2 W/T group. However, other studies disagree: Kouroupi et al () found no difference in the 46/1 haplotype frequency amongst 170 V617F + versus W/T SVT patients ( P = 0·9). These differences can partly be attributed to differences in JAK2 burdens between patients; those with lower allele burdens express 46/1 haplotype frequencies similar to V617F‐negative patients.…”

Section: Individual Risk Factors For Svtmentioning

confidence: 96%

Splanchnic vein thrombosis in myeloproliferative neoplasms

2013

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SummarySplanchnic vein thrombosis (SVT) is one of the most important complications of myeloproliferative neoplasms (MPN). Although MPN are common causes of SVT, the pathophysiological mechanisms underlying this predisposition, their epidemiology and natural history are not fully understood. Studies have concentrated on the generalized prothrombotic environment generated by MPN and their relationship with abnormal blood counts, thereby furthering our knowledge of arterial and venous thrombosis in this population. In contrast, there are few studies that have specifically addressed SVT in the context of MPN. Recent research has demonstrated in patients with MPN the existence of factors increasing the risk of SVT such as the presence of the JAK2 V617F mutation and its 46/1 haplotype. Features unique to the circulating blood cells, splanchnic vasculature and surrounding micro-environment in patients with MPN have been described. There are also abnormalities in local haemodynamics, haemostatic molecules, the spleen, and splanchnic endothelial and endothelial progenitor cells. This review considers these important advances and discusses the contribution of individual anomalies that lead to the development of SVT in both the pre-neoplastic and overt stage of MPN. Clinical issues relating to epidemiology, recurrence and survival in these patients have also been reviewed and their results discussed.

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The JAK2 46/1 haplotype in splanchnic vein thrombosis

Abstract: References

Cited by 13 publications

References 11 publications

Association between JAK2 rs4495487 Polymorphism and Risk of Budd-Chiari Syndrome in China

Association between JAK2 rs4495487 Polymorphism and Risk of Budd-Chiari Syndrome in China

The C allele of JAK2 rs4495487 is an additional candidate locus that contributes to myeloproliferative neoplasm predisposition in the Japanese population

Splanchnic vein thrombosis in myeloproliferative neoplasms

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