Abstract
The telomerase reverse transcriptase (TERT) gene rs2736100_C allele has recently been shown to be associated with an increased risk for myeloproliferative neoplasms (MPNs) among Caucasians. However, it is unknown if this association is present in other ethnical populations and whether rs2736100 allele frequencies mirror the incidence of MPNs in a population. Here we genotyped TERT rs2736100 variants in 126 Swedish and 101 Chinese MPN patients and their age-, sex-, and ethnically-matched healthy controls. Healthy Chinese adults had a higher frequency of the A allele and lower frequencies of the C allele compared to Swedish counterparts (57.4 vs 47.0 % for A, 42.6 vs 53.0 % for C, P = 0.006). Both Swedish and Chinese patients harbored significantly higher C allele frequency than their controls (62.7 vs 53.0 % and 57.4 vs 42.6 % for Swedish and Chinese, respectively, P = 0.004). Swedes and Chinese bearing the CC genotype had a significantly increased risk of MPN compared to AA carriers (OR = 2.47; 95 % CI: 1.33–4.57, P = 0.003, for Swedes, and OR = 3.45; 95 % CI: 1.52–7.85, P = 0.005, for Chinese). Further analyses showed that rs2736100_CC was associated with robustly enhanced risk in males only (CC vs AA, OR = 5.11; 95 % CI: 2.19–11.92, P < 0.0001). The CC-carrying MPN patients exhibited significantly higher TERT expression than patients with the AC genotype. Collectively, the rs2736100_C is a risk allele for MPNs in Swedish and Chinese males, and the lower incidence of MPNs in the Chinese population is correlated with a lower rs2736100_C risk allele frequency.
Highlights
Philadelphia chromosome negative myeloproliferative neoplasms (MPNs), consisting of polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are characterized by hyperproliferation in the bone marrow leading to an excessive amount of mature cells from one or more of the myeloid lineages [1]
A number of issues remain to be defined: first, it is well known that racial disparities exists in both germline and somatic genetic alterations in the pathogenesis of cancer [22]
It is important to evaluate whether the correlation between rs2736100 allele variant and risk of MPN is observed in other ethnic populations
Summary
Philadelphia chromosome negative myeloproliferative neoplasms (MPNs), consisting of polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are characterized by hyperproliferation in the bone marrow leading to an excessive amount of mature cells from one or more of the myeloid lineages [1]. Several genetic alterations have been identified in MPNs, with the most common being the JAK2V617F mutation seen in 95 % of PV and 50 % of ET and PMF. 70 and 10 % of JAK2V617F-negative ET and PMF, respectively [1, 4,5,6]. The identification of these mutations provides profound insights into the pathogenesis of MPNs, but the exact etiology remains incompletely understood. The MPN incidence varies significantly dependent on geographical areas, from approximately 2/100,000 person-years in China [7] to 5.8/100,000 person-years in Europe [1, 8], which highlights differences in genetic susceptibility. Little is known about genetic events underlying this difference in incidence between Caucasians and Chinese
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