258O - A germline variant rs2736098 in the TERT gene is a novel predisposition allele associated with JAK2V617F-positive myeloproliferative neoplasms

Background

Myeloproliferative neoplasms (MPN) are a group of blood malignancies proliferating clonally and driven by somatic mutations in JAK2, CALR or MPL gene, but the contribution of genetic polymorphisms is not well characterized. Several germline variations at the JAK2 and TERT genes have been identified to be associated with MPN in different ethnic populations. Based on the previous studies, it has been established that rs2736100, rs2853677 and rs7705526 of TERT gene have strong association with MPN. The aim of this study was to identify any novel single-nucleotide polymorphism (SNP) in the TERT gene that may have any association with JAK2V617F-positive MPN.

Methods

Here we genotyped 4 TERT variants (rs2736100, rs2853677, rs7705526 and rs2736098) in 137 Hong Kong Chinese JAK2V617F-positive MPN patients and 480 ethnically matched healthy controls by unlabelled probe melting analysis technique.

Results

The genotyping analysis for these 4 SNPs with allelic model showed strong association (P < 0.05) with JAK2V617F-positive MPN. In addition, we found rs2736098, a novel SNP that also showed a strong association with JAK2V617F-positive MPN (P = 0.0006). We also observed a very strong association after performing allele association test with 50000 permutations in single marker analysis (P_emp = 0.003). For non-synonymous SNP rs2736098 the minor allele ‘T’ was found to be a risk allele (OR: 1.59, 95% CI: 1.22-2.09; P = 0.004) after adopting the logistic regression with age and sex adjustment.

Conclusions

Our findings suggest that the rs2736098 variant of TERT gene is associated with an increased risk of JAK2V617F-positive MPN in Hong Kong Chinese patients, indicating that rs2736098 might be a unique and potential signature for predicting the risk of JAK2V617F-positive MPN in Hong Kong Chinese population. To strengthen our findings worldwide, it is required to conduct similar studies in different ethnicity with a larger sample size.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

The Hong Kong Polytechnic University, Hong Kong SAR, China.

Disclosure

All authors have declared no conflicts of interest.