Characterization of JAK2V617F and the JAK2 46/1 germline haplotype in myeloproliferative neoplasms in a Saudi Arabian cohort: a case-based analysis

Background JAK2V617F is an important mutation associated with myeloproliferative neoplasms (MPNs). The germline JAK2 46/1 haplotype is an established low-penetrance predisposition factor for MPNs across multiple ethnicities. This study aimed to characterize JAK2V617F mutation prevalence and JAK2 46/1 haplotype distribution in a Saudi Arabian MPN cohort. Methods A retrospective cohort study was conducted at King Fahad Medical City, Riyadh, Saudi Arabia. A total of 130 participants (98 MPN patients and 32 non-MPN controls) were enrolled between January 2018 and December 2019. JAK2V617F mutation status was determined by allele-specific TaqMan qPCR. SNPs rs12343867 and rs10974900 were genotyped using validated TaqMan SNP assays to define haplotype carrier status. Results JAK2V617F was detected in 13.1% of patients (n=17; 9 females, 8 males), with no statistically significant sex-based difference in mutation frequency. At rs12343867, the aggregate 46/1 haplotype carrier frequency was 80.7% (homozygous TT: 51.5%; heterozygous CT: 29.2%). By MPN subtype, TT homozygosity was most prevalent in ET (56.3%). By MPN subtype, the CC genotype predominated in ET (57.8%), PV (50.0%), PMF (75.0%), and non-MPN controls (54.8%). Conclusions This is the first study to simultaneously characterize JAK2V617F and the germline JAK2 46/1 haplotype in a Saudi Arabian MPN cohort. The elevated haplotype carrier frequency supports an inherited predisposition to MPN in this population and positions the JAK2 46/1 haplotype as a candidate supplementary biomarker for risk stratification. Prospective, multi-centre studies incorporating comprehensive driver mutation profiling and population-matched healthy controls are warranted.