The JAK2 46/1 haplotype in Budd-Chiari syndrome and portal vein thrombosis

Blood ◽  
2011 ◽  
Vol 117 (15) ◽  
pp. 3968-3973 ◽  
Author(s):  
Jasper H. Smalberg ◽  
Edith Koehler ◽  
Sarwa Darwish Murad ◽  
Aurelie Plessier ◽  
Susana Seijo ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Portal Vein ◽  
Clinical Presentation ◽  
Myeloproliferative Neoplasms ◽  
Nucleotide Polymorphism ◽  
Budd Chiari Syndrome ◽  
Single Nucleotide ◽  
Vein Thrombosis ◽  
Chiari Syndrome

Abstract The germline JAK2 46/1 haplotype has been associated with the development of JAK2V617F-positive as well as JAK2V617F-negative myeloproliferative neoplasms (MPNs). In this study we examined the role of the 46/1 haplotype in the etiology and clinical presentation of patients with splanchnic vein thrombosis (SVT), in which MPNs are the most prominent underlying etiological factor. The single-nucleotide polymorphism rs12343867, which tags 46/1, was genotyped in 199 SVT patients. The 46/1 haplotype was overrepresented in JAK2V617F-positive SVT patients compared with controls (P < .01). Prevalence of the 46/1 haplotype in JAK2V617F-negative SVT patients did not differ from prevalence in the controls. However, JAK2V617F-negative SVT patients with a proven MPN also exhibited an increased frequency of the 46/1 haplotype (P = .06). Interestingly, 46/1 was associated with increased erythropoiesis in JAK2V617F-negative SVT patients. We conclude that the 46/1 haplotype is associated with the development of JAK2V617F-positive SVT. In addition, our findings in JAK2V617F-negative SVT patients indicate an important role for the 46/1 haplotype in the etiology and diagnosis of SVT-related MPNs, independent of JAK2V617F, that requires further exploration.

JAK2 Germline Genetic Variation In Budd-Chiari Syndrome and Portal Vein Thrombosis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4212-4212
Author(s):  
Jasper Smalberg ◽  
Edith Koehler ◽  
Sarwa Darwish Murad ◽  
Aurelie Plessier ◽  
Juan-Carlos Garcia-Pagan ◽  
...  
Keyword(s):  
Portal Vein ◽  
Portal Vein Thrombosis ◽  
Conflicts Of Interest ◽  
Myeloproliferative Neoplasms ◽  
Jak2 V617f ◽  
Budd Chiari Syndrome ◽  
Single Nucleotide ◽  
Vein Thrombosis ◽  
Chiari Syndrome

Abstract Abstract 4212 Primary Budd-Chiari syndrome (BCS) and non-malignant, non-cirrhotic portal vein thrombosis (PVT) are rare disorders with a considerable overlap in etiology. Myeloproliferative neoplasms (MPN) are the most frequent underlying prothrombotic factor in both entities. The JAK2 V617F mutation (VF) has been identified in over half of the individuals with MPN. Recently, a JAK2 haplotype, designated ‘46/1’, has been described. Previous studies suggest that the JAK2 46/1 haplotype represents a disease susceptibility to MPN, independent of VF status. The aim of this study was to determine the role of the JAK2 46/1 haplotype in the etiology of BCS and PVT. Patients were recruited from the EN-Vie cohort, consisting of 163 BCS and 138 PVT patients, consecutively enrolled in nine European countries between October 2003 and October 2005. DNA was available from 116 BCS patients (50 males and 66 females; median age 38.1), 97 PVT patients (47 males and 50 females; median age 49.8) and 104 healthy controls (43 males and 61 females; median age 36.8). The JAK2 46/1 haplotype was tagged by the rs12343867 single nucleotide polymorphism. Frequency of the JAK2 haplotype 46/1 was higher in BCS (36%, p=0.06) compared to controls (27%), while similar in PVT patients (28%, p=0.89). When stratified for VF status, haplotype 46/1 frequency was higher in VF positive BCS (44%, p=0.01) and VF positive PVT patients (40%, p=0.06) compared to controls. Haplotype 46/1 frequency was similar in VF negative BCS (33%, p=0.29) and PVT patients (24%, p=0.47) compared to controls. VF negative BCS patients with a proven MPN also showed increased frequency of the 46/1 haplotype (56%, p=0.07). Logistic regression, adjusted for age and sex, showed an association between the 46/1 haplotype and risk of VF positive BCS (OR: 2.10; 1.16–3.80), VF positive PVT (OR 2.07; 0.95–4.52) and VF negative BCS patients with a proven MPN (OR 3.04; 1.02–9.06). We conclude that the JAK2 46/1 haplotype may be associated with BCS and that this was limited to patients with a proven MPN, independent of VF status. In PVT, the 46/1 haplotype was only associated with patients who were VF positive. This study was carried out on behalf of the European Network for Vascular Disorders of the Liver (EN-Vie). Disclosures: No relevant conflicts of interest to declare.

Myeloproliferative neoplasms in Budd-Chiari syndrome and portal vein thrombosis: a meta-analysis

Blood ◽  
2012 ◽  
Vol 120 (25) ◽  
pp. 4921-4928 ◽  
Author(s):  
Jasper H. Smalberg ◽  
Lidia R. Arends ◽  
Dominique C. Valla ◽  
Jean-Jacques Kiladjian ◽  
Harry L. A. Janssen ◽  
...  
Keyword(s):  
Portal Vein ◽  
Portal Vein Thrombosis ◽  
Myeloproliferative Neoplasms ◽  
Meta Analysis ◽  
Random Effects Model ◽  
Budd Chiari Syndrome ◽  
Vein Thrombosis ◽  
High Prevalence ◽  
Diagnostic Role ◽  
Chiari Syndrome

Abstract Myeloproliferative neoplasms (MPNs) are the most common cause of Budd-Chiari syndrome (BCS) and nonmalignant, noncirrhotic portal vein thrombosis (PVT). In this meta-analysis, we determined the prevalence of MPNs and their subtypes as well as JAK2V617F and its diagnostic role in these uncommon disorders. MEDLINE and EMBASE databases were searched. Prevalence of MPNs, JAK2V617F, and MPN subtypes were calculated using a random-effects model. A total of 1062 BCS and 855 PVT patients were included. In BCS, mean prevalence of MPNs and JAK2V617F was 40.9% (95% CI, 32.9%-49.5%) and 41.1% (95% CI, 32.3%-50.6%), respectively. In PVT, mean prevalence of MPNs and JAK2V617F was 31.5% (95% CI, 25.1%-38.8%) and 27.7% (95% CI, 20.8%-35.8%), respectively. JAK2V617F and MPNs were more frequent in BCS compared with PVT (P = .03 and P = .09, respectively). Polycythemia vera was more prevalent in BCS than in PVT (P = .001). JAK2V617F screening in splanchnic vein thrombosis (SVT) patients without typical hematologic MPN features identified MPN in 17.1% and 15.4% of screened BCS and PVT patients, respectively. These results demonstrate a high prevalence of MPNs and JAK2V617F in SVT patients and show differences in underlying etiology between these disorders. Furthermore, these results validate routine inclusion of JAK2V617F in the diagnostic workup of SVT patients.

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

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Peijin Zhang ◽  
Yanyan Zhang ◽  
Jing Zhang ◽  
Hui Wang ◽  
He Ma ◽  
...  
Keyword(s):  
Clinical Presentation ◽  
Myeloproliferative Neoplasms ◽  
Jak2 V617f ◽  
Recessive Model ◽  
Elevated Risk ◽  
Budd Chiari Syndrome ◽  
Candidate Locus ◽  
Susceptibility Factor ◽  
Chiari Syndrome

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.

891 PIVOT ROLE OF PAI 1 4G4G IN NON-CIRRHOTIC PORTAL VEIN THROMBOSIS AND BUDD-CHIARI SYNDROME

2011 ◽  
Vol 54 ◽  
pp. S355 ◽  
Author(s):  
M. D'Amico ◽  
M. Niceta ◽  
P. Sammarco ◽  
R. Virdone ◽  
E. Sinagra
Keyword(s):  
Portal Vein ◽  
Portal Vein Thrombosis ◽  
Budd Chiari Syndrome ◽  
Vein Thrombosis ◽  
Chiari Syndrome ◽  
Pai 1

Splanchnic vein closures

2019 ◽  
Vol 98 (6) ◽  
pp. 239-244
Keyword(s):  
Portal Vein ◽  
Surgical Approach ◽  
Medical Problem ◽  
Budd Chiari Syndrome ◽  
Extrahepatic Portal Vein Obstruction ◽  
Mesenteric Vein ◽  
Vein Thrombosis ◽  
Portal Vein Obstruction ◽  
Chiari Syndrome ◽  
Outflow System

Closures in the splanchnic venous system (SVS) represent a broad medical problem. Anatomically, individual or even multiple sections of SVS may be affected at the same time. Main sections of SVS include the venous liver outflow system, the portal vein, and the upper mesenteric vein and its basin. Thrombosis is clearly the predominant cause of closure. The closures can present as acute, subacute, chronic occult or chronic manifest. The main pathological and anatomical units are the Budd-Chiari syndrome (BCS), extrahepatic portal vein obstruction (EHPVO) and mesenteric vein thrombosis (MVT). Advanced laboratory, imaging and intervention methods substantially modify the approach to prevention, diagnosis and treatment; surgical approach also plays a role. The problem of SVS closures is interdisciplinary.

scholarly journals Prevalence of ACSL (rs6552828) polymorphism among runners

2019 ◽  
Vol 24 ◽  
pp. 121-128
Author(s):  
Sigal Ben-Zaken ◽  
Yoav Meckel ◽  
Dan Nemet ◽  
Alon Eliakim
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Genetic Basis ◽  
Maximal Oxygen Consumption ◽  
Professional Athletes ◽  
Distance Runners ◽  
Nucleotide Polymorphism ◽  
Long Distance ◽  
Single Nucleotide ◽  
The Common

The ACSL A/G polymorphism is associated with endurance trainability. Previous studies have demonstrated that homozygotes of the minor AA allele had a reduced maximal oxygen consumption response to training compared to the common GG allele homozygotes, and that the ACSL A/G single nucleotide polymorphism explained 6.1% of the variance in the VO2max response to endurance training. The contribution of ACSL single nucleotide polymorphism to endurance trainability was shown in nonathletes, however, its potential role in professional athletes is not clear. Moreover, the genetic basis to anaerobic trainability is even less studied. Therefore, the aim of the present study was to examine the prevalence of ACSL single nucleotide polymorphism among professional Israeli long distance runners (n=59), middle distance runners (n=31), sprinters and jumpers (n=48) and non-athletic controls (n=60). The main finding of the present study was that the ACSL1 AA genotype, previously shown to be associated with reduced endurance trainability, was not higher among sprinters and jumpers (15%) compared to middle- (16%) and long-distance runners (15%). This suggests that in contrast to previous studies indicating that the ACSL1 single nucleotide polymorphism may influence endurance trainability among non-athletic individuals, the role of this polymorphism among professional athletes is still not clear.

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