Prevalence and phenotypes of JAK2V617F and calreticulinmutations in a Danish general population

The JAK2V617F and calreticulinmutations (CALR) are frequent within myeloproliferative neoplasms (MPNs). JAK2V617F has been detected in the general population, but no studies have previously investigated the CALRprevalence. Thus, we aimed to determine the CALRand JAK2V617F population prevalence and assess the biochemical profile and lifestyle factors in mutation-positive individuals with and without MPN. 19 958 eligible participants, enrolled from 2010-2013, from the Danish General Suburban Population Study were screened for JAK2V617F and CALRby droplet digital polymerase chain reaction with (3.2%) mutation positives of which 16 (2.5%) had MPN at baseline. Of 645 participants, 613 were JAK2V617F positive, and 32 were CALRpositive, corresponding to a population prevalence of 3.1% (confidence interval [CI], 2.8-3.3) and 0.16% (CI, 0.11-0.23), respectively. Increasing age, smoking, and alcohol were risk factors for the mutations. JAK2V617F positives with and without MPN presented elevated odds for prevalent venous thromboembolism. The odds ratio for a diagnosis of MPN per percentage allele burden was 1.14 (95% CI, 1.09-1.18; P= 1.6 × 10−10). Mutation positives displayed higher blood cell counts than nonmutated participants, and 42% of mutation positives without MPN presented elevation of ≥1 blood cell counts; 80 (13%) even presented blood cell counts in accordance with current MPN diagnostic criteria. In conclusion, we present a novel population prevalence of CALRand a JAK2V617F prevalence that is 3 to 30 times higher compared with less sensitive methods. Mutation-positive non-MPNs with elevated blood cell counts raise concerns of MPN underdiagnosis in the population.