title: The association of the JAK2 46/1 haplotype with non-splanchnic venous thrombosis.
abstract: BACKGROUND
  The inherited JAK2 46/1 haplotype is strongly associated with the development of myeloproliferative neoplasms (MPNs), and its increased frequency has also been reported in splanchnic venous thrombosis (SVT). In the present study, the role of the JAK2 46/1 haplotype in non-splanchnic venous thrombosis (non-SVT) was investigated.
  
  
  RESULTS
  We genotyped 438 patients with non-SVT, 226 patients with MPNs and 459 healthy controls for three single nucleotide polymorphisms (SNPs) which tag the JAK2 46/1 haplotype (rs12342421 G>C, rs12343867 T>C and rs10974944 C>G). We found statistically significant association of the rs12342421 GC+CC genotypes (OR=1.40; p=0.023) and the rs12343867 TC+CC genotypes (OR=1.83; p=7.02 x 10(-5)) with non-SVT. We also found that the CC haplotype of these two SNPs was associated with an increased risk of the disease (OR=1.68; p=0.009). Stratification analysis indicated that the observed association of the JAK2 46/1 haplotype with non-SVT was probably largely free of confounding effect of thrombophilic risk factors. In addition, we established a strong association of SNPs rs12342421 and rs10974944 and their CG haplotype with MPNs and with JAK2 V617F-positive MPNs.
  
  
  CONCLUSIONS
  This study provides statistical evidence that SNPs rs12342421 and rs12343867 are associated with an increased risk of non-SVT. Consistently, haplotypes of the SNPs were also associated with non-SVT risk, suggesting that inherited genetic variation in the JAK2 gene may play a role in the pathogenesis of non-SVT. Furthermore, the reported associations of the JAK2 46/1 haplotype with MPNs as well as with the occurrence of the JAK2 V617F mutation in MPNs were confirmed.
authors.affiliation: Laboratory of Medical Genetics, University Medical Centre Maribor, Slovenia. Electronic address: kzerjavic@gmail.com.
authors.forename: Katja
authors.initials: K
authors.lastname: Zerjavic
authors.forename: Boris
authors.initials: B
authors.lastname: Zagradisnik
authors.forename: Lidija
authors.initials: L
authors.lastname: Lokar
authors.forename: Marjana G
authors.initials: MG
authors.lastname: Krasevac
authors.forename: Nadja K
authors.initials: NK
authors.lastname: Vokac
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000201:enzymology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D020246:Venous Thrombosis / Q000201:enzymology* / Q000235:genetics*; D055815:Young Adult
chemical_list: C507924:JAK2 protein, human; D053614:Janus Kinase 2
keywords: AS-PCR; Association study; CI; ET; FDR; HWE; Hardy-Weinberg equilibrium; JAK2; JAK2 46/1 haplotype; JAK2 V617F mutation; Janus kinase 2; MPNs; Myeloproliferative neoplasms; Non-splanchnic venous thrombosis; OR; PMF; PV; SNP; SVT; allele-specific polymerase chain reaction; confidential interval; essential thrombocythaemia; false discovery rate; myeloproliferative neoplasms; non-SVT; non-splanchnic venous thrombosis; odds ratio; polycythaemia vera; primary myelofibrosis; single nucleotide polymorphism; splanchnic venous thrombosis