Distribution of Variant rs10974944 of the JAK2 Gene in Mestizos and Native Americans from Mexico and from Worldwide Association Studies of Myeloproliferative Diseases

The genetic variant rs10974944 (C>G) in the JAK2 gene is associated with a higher risk of myeloproliferative neoplasms (MPNs) by increasing the probability of the somatic mutation V617F in the JAK2 protein. For this reason, we evaluated the distribution of rs10974944 in Mexican populations, including published data from association studies in worldwide populations. We analyzed five Mestizo (admixed; n = 200) and four Native American (n = 200) population samples from Mexico, representing the northern, central, western, and southern regions of the country, genotyping rs10974944 by quantitative PCR using Taqman probes. Allele and genotype frequencies were estimated in each population sample. The wild-type allele C, the homozygous C/C, and the heterozygous C/G variants were the most frequent in all Mexican populations, and the genotype distribution in all samples was in Hardy-Weinberg equilibrium. Interestingly, genetic distances clustered most of the worldwide patient samples, including Tarahumaras and Mayas, which differed from Mexican and control samples. Although higher genetic susceptibility to MPNs could be predicted in these Native American populations, the homogeneous allele distribution among Mexican and worldwide control populations warrants analysis of further genetic and nongenetic factors. In sum, although worldwide population samples displayed homogeneous distribution for rs10974944 , genetic clustering of worldwide patients supports the claimed association with MPNs.