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Genotyping Helps Avoid Needless Bone Marrow Biopsies in African-Americans

By LabMedica International staff writers
Posted on 13 Jul 2021
Bone marrow biopsies may be used unnecessarily in some African American individuals who are genetically predisposed to having relatively low white blood cell counts.

The rs2814778 genotype is within the DARC gene, which encodes the Duffy blood group antigen. More...
This single nucleotide polymorphism (SNP) shows an almost perfectly fixed difference in frequency between Europeans and those with African ancestry. (One exception appears to be a certain population of Czech gypsies, and certain non-Ashkenazi Jewish populations.)

A team of medical scientists led by the Vanderbilt University Medical Center group (Nashville, TN, USA) carried out a genetic association study, among 399 African- American individuals who underwent a bone marrow biopsy as part of routine clinical care at three medical centers, from January 1, 1998, to December 31, 2020. The rs2814778-CC genotype was highly prevalent when the biopsy was performed to evaluate isolated low WBC counts. In the absence of another cell type abnormality, these biopsies very rarely identified a hematologic abnormality.

The team reported that the rs2814778-CC genotype, previously linked to low white blood cell counts, was present in some 67% of the individuals who were referred for bone marrow biopsies based on their medical history, beyond low white blood cell counts alone. In contrast, the team noted that the rs2814778-CC genotype turned up in all but one of the 35 patients who underwent bone marrow biopsies solely based on lower-than-usual white blood cell counts. Those results hinted that testing may have been unnecessary in this small subset of patients, particularly since 97% of them had normal biopsy results, compared to 55% in the subset of 243 African American patients who did not carry the rs2814778-CC genotype.

The study found that white blood cell counts may be low due to an rs2814778-CC variant in the promoter of the atypical chemokine receptor 1-coding gene (ACKR1). Among 399 individuals who underwent a bone marrow biopsy (BMB) (mean ± SD, age, 41.8 ± 22.5years, 234 [59%] female), 277 (69%) had the CC genotype. A total of 35 patients (9%) had clinical histories of isolated low WBC counts, and 364 (91%) had other histories. Of those with a clinical history of isolated low WBC count, 34 of 35 (97%) had the CC genotype versus 243 of 364 (67%) of those without a low WBC count history. Among those with the CC genotype, 33 of 34 (97%) had normal results for biopsies performed for isolated low WBC counts compared with 134 of 243 individuals (55%) with biopsies performed for other histories.

Jonathan D. Mosley, MD, PhD, an Assistant Professor and a senior author of the study, said, “We've essentially created this racial health disparity by not fully considering how genetic variation affects white blood cell levels. Our study supports genotyping African Americans before performing a bone marrow biopsy for the indication of isolated low white blood cell counts.”

The authors concluded that in this genetic association study, among patients of African American race who had a BMB with a clinical history of isolated low WBC counts, the rs2814778-CC genotype was highly prevalent, and 97% of these BMBs identified no hematologic abnormality. Accounting for the rs2814778-CC genotype in clinical decision-making could avoid unnecessary BMB procedures. The study was published on June 28, 2021 in the journal JAMA Internal Medicine.

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Vanderbilt University Medical Center group


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