The association of the JAK2 46/1 haplotype with non-splanchnic venous thrombosis.
Thromb Res
; 132(2): e86-93, 2013 Aug.
Article
em En
| MEDLINE
| ID: mdl-23845539
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. METHODS ANDRESULTS:
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.Palavras-chave
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
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Trombose Venosa
/
Janus Quinase 2
Tipo de estudo:
Etiology_studies
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Observational_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article