Credit: Jeremy L. Grisham
An analysis of more than 30,000 individuals has revealed several genetic mutations that appear to play roles in hematologic disorders.
Investigators discovered variants that showed correlations with platelet counts, white blood cell (WBC) counts, hemoglobin concentration, and hematocrit levels.
The group believes these findings could have implications for a range of conditions, including cytopenias, myeloproliferative neoplasms, and stroke.
Guillaume Lettre, PhD, of Université de Montréal and the Montreal Heart Institute in Canada, and his colleagues recounted their discoveries in a letter to Nature Genetics.
The investigators analyzed hemoglobin concentration, hematocrit levels, WBC counts, and platelet counts in 31,340 individuals genotyped on an exome array.
This revealed several missense variants in CXCR2 that were associated with a decreased WBC count. And in a resequencing study, the team identified a CXCR2 frameshift mutation that was associated with congenital neutropenia.
The group also discovered several missense and splice-site variants in genes known to regulate hematopoiesis—TFR2, HBB, TUBB1, SH2B3, and EPO.
A TFR2 mutation (rs139178017) was independently associated with higher hematocrit levels and hemoglobin concentration.
An HBB variant (rs33971440) and an EPO variant (rs62483572), on the other hand, were associated with lower hematocrit levels and hemoglobin concentrations. Further analyses confirmed that having these mutations increased a person’s risk of anemia, with odds ratios of 36.1 and 1.7, respectively.
A TUBB1 missense variant (rs41303899) was associated with decreased platelet count, while 2 missense variants of SH2B3 (rs148636776 and rs72650673) were associated with increased platelet counts.
Lastly, a mutation in JAK2 (rs77375493) was associated with increases in platelets, WBCs, hemoglobin, and hematocrit. And further analyses suggested that individuals with this variant had early stage myeloproliferative neoplasms.
“[T]hese donors also had a higher risk of having a stroke during their lifetime,” said study author Jean-Claude Tardif, MD, of Université de Montréal and the Montreal Heart Institute.
He and his colleagues believe these findings are encouraging, as they provide additional insight into hematologic disorders. But the results also suggest the experimental approach used in this study can be applied to other diseases as well.
