English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

Background  Myeloproliferative neoplasms (MPNs) are a group of haematological malignancies that can be characterised by a somatic mutation ( JAK2V617F ). This mutation causes the bone marrow to produce excessive blood cells and is found in polycythaemia vera (~95%), essential thrombocythaemia and primary myelofibrosis (both ~50%). It is considered as a major genetic factor contributing to the development of these MPNs. No genetic association study of MPN in the Hong Kong population has so far been reported. Here, we investigated the relationship between germline  JAK2  polymorphisms and MPNs in Hong Kong Chinese to find causal variants that contribute to MPN development. We analysed 19 tag single nucleotide polymorphisms (SNPs) within the  JAK2  locus in 172 MPN patients and 470 healthy controls. Three of these 19 SNPs defined the reported  JAK2  46/1 haplotype: rs10974944, rs12343867 and rs12340895. Allele and haplotype frequencies were compared between patients and controls by logistic regression adjusted for sex and age. Permutation test was used to correct for multiple comparisons. With significant findings from the 19 SNPs, we then examined 76 additional SNPs across the 148.7-kb region of  JAK2  via imputation with the SNP data from the 1000 Genomes Project.    Results  In single-marker analysis, 15 SNPs showed association with  JAK2V617F -positive MPNs (n = 128), and 8 of these were novel MPN-associated SNPs not previously reported. Exhaustive variable-sized sliding-window haplotype analysis identified 184 haplotypes showing significant differences ( P  < 0.05) in frequencies between patients and controls even after multiple-testing correction. However, single-marker alleles exhibited the strongest association with  V617F -positive MPNs. In local Hong Kong Chinese, rs12342421 showed the strongest association signal: asymptotic  P  = 3.76 × 10 −15 , empirical  P  = 2.00 × 10 −5  for 50,000 permutations, OR = 3.55 for the minor allele  C , and 95% CI, 2.59-4.87. Conditional logistic regression also signified an independent effect of rs12342421 in significant haplotype windows, and this independent effect remained unchanged even with the imputation of additional 76 SNPs. No significant association was found between  V617F -negative MPNs and  JAK2  SNPs.    Conclusion  With a large sample size, we reported the association between  JAK2V617F -positive MPNs and 15 tag  JAK2  SNPs and the association of rs12342421 being independent of the  JAK2  46/1 haplotype in Hong Kong Chinese population.    Electronic supplementary material  The online version of this article (doi:10.1186/s12863-014-0147-y) contains supplementary material, which is available to authorized users.

Genetic association between germline JAK2polymorphisms and myeloproliferative neoplasms in Hong Kong Chinese population: a case–control study