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The JAK2 46/1 haplotype (GGCC) in myeloproliferative neoplasms and splanchnic vein thrombosis: a pooled analysis of 26 observational studies

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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.

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Acknowledgments

This study was supported in part by the National Natural Science Foundation of China (no. 81172604). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. All authors critically reviewed the manuscript for important intellectual content and approved the final manuscript.

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No potential conflicts of interest relevant to this article were reported.

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  1. Statistics Office of Information Center, The Affiliated Hospital of Xu Zhou Medical College, 99# Huai-hai West Road, 221006, Xuzhou, China

    Sheng-li Li

  2. School of Public Health, Xuzhou Medical College, 209# Tong-shan Road, 221004, Xuzhou, China

    Pei-jin Zhang, Gui-xiang Sun & Zhao-jun Lu

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Li, Sl., Zhang, Pj., Sun, Gx. et al. The JAK2 46/1 haplotype (GGCC) in myeloproliferative neoplasms and splanchnic vein thrombosis: a pooled analysis of 26 observational studies. Ann Hematol 93, 1845–1852 (2014). https://doi.org/10.1007/s00277-014-2134-9

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