title: The JAK2 46/1 haplotype (GGCC) in myeloproliferative neoplasms and splanchnic vein thrombosis: a pooled analysis of 26 observational studies.
abstract: Numbers of observational studies suggest that the JAK2 46/1 (GGCC) haplotype may increase the risk of myeloproliferative neoplasms (MPNs) and splanchnic vein thrombosis (SVT), but the results remain controversial. We aimed to examine the association between the JAK2 46/1 haplotype and risk of MPNs and SVT by conducting a meta-analysis. PubMed, EMBASE, Cochrane Library, CBM, and CNKI databases were searched to identify eligible studies without restrictions and by reviewing reference lists of obtained articles. Both fixed and random-effects models were used to calculate the summary risk estimates. We identified 26 observational studies of the JAK2 46/1 haplotype and risk of MPNs and SVT involving 8,561 cases and 7,434 participants. In the overall analysis, it was found that the JAK2 46/1 haplotype significantly elevated the risk of MPNs (rs10974944: C vs T: odds ratio (OR) = 2.19, 95 % confidence interval (CI) = 1.86-2.57, P < 0.0001; CC vs TT: OR = 4.63, 95 % CI = 3.32-6.47, P < 0.0001; CT vs TT: OR = 2.49, 95 % CI = 2.11-2.95, P < 0.0001; (CC + CT) vs TT: OR = 2.92, 95 % CI = 2.51-3.39, P < 0.0001; rs12343867: C vs T: OR = 1.88, 95 % CI = 1.59-2.22, P < 0.0001; CC vs TT: OR = 3.16, 95 %CI = 2.14-4.65, P < 0.0001; CT vs TT: OR = 2.04, 95 % CI = 1.51-2.74, P < 0.0001; (CC + CT) vs TT: OR = 2.25, 95 % CI = 1.73-2.95, P < 0.0001) and SVT (C vs T: OR = 1.27, 95 % CI = 1.06-1.52, P = 0.011; CC vs TT: OR = 2.33, 95 % CI = 1.42-3.81, P = 0.001; (CC + CT) vs TT: OR = 1.25, 95 % CI = 1.02-1.53, P = 0.034). There was no evidence of a significant association between the rs12343867 and the risk of SVT in the genetic model (CT vs TT: OR = 1.01, 95 % CI = 0.80-1.29, P = 0.906). This meta-analysis provides new evidence supporting the conclusion that the JAK2 46/1 haplotype enrichment is significantly associated with the development of MPNs and SVT in these patients.
authors.affiliation: Statistics Office of Information Center, The Affiliated Hospital of Xu Zhou Medical College, 99# Huai-hai West Road, 221006, Xuzhou, China, lishengli401@163.com.
authors.forename: Sheng-Li
authors.initials: SL
authors.lastname: Li
authors.forename: Pei-Jin
authors.initials: PJ
authors.lastname: Zhang
authors.forename: Gui-Xiang
authors.initials: GX
authors.lastname: Sun
authors.forename: Zhao-Jun
authors.initials: ZJ
authors.lastname: Lu
mesh_terms: D019046:Bone Marrow Neoplasms / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics* / Q000378:metabolism; D009196:Myeloproliferative Disorders / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics; D064887:Observational Studies as Topic / Q000379:methods; D013152:Splanchnic Circulation / Q000502:physiology*; D020246:Venous Thrombosis / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*
chemical_list: C507924:JAK2 protein, human; D053614:Janus Kinase 2