Association Between a Common, Benign Genotype and Unnecessary Bone Marrow Biopsies Among African American Patients

JAMA Intern Med. 2021 Aug 1;181(8):1100-1105. doi: 10.1001/jamainternmed.2021.3108.

Abstract

Importance: Up to two-thirds of African American individuals carry the benign rs2814778-CC genotype that lowers total white blood cell (WBC) count.

Objective: To examine whether the rs2814778-CC genotype is associated with an increased likelihood of receiving a bone marrow biopsy (BMB) for an isolated low WBC count.

Design, setting, and participants: This retrospective genetic association study assessed African American patients younger than 90 years who underwent a BMB at Vanderbilt University Medical Center, Mount Sinai Health System, or Children's Hospital of Philadelphia from January 1, 1998, to December 31, 2020.

Exposure: The rs2814778-CC genotype.

Main outcomes and measures: The proportion of individuals with the CC genotype who underwent BMB for an isolated low WBC count and had a normal biopsy result compared with the proportion of individuals with the CC genotype who underwent BMB for other indications and had a normal biopsy result.

Results: Among 399 individuals who underwent a BMB (mean [SD] age, 41.8 [22.5] years, 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 vs 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 (P < .001).

Conclusions and relevance: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biopsy* / methods
  • Biopsy* / statistics & numerical data
  • Black or African American / genetics*
  • Bone Marrow Examination* / methods
  • Bone Marrow Examination* / statistics & numerical data
  • Duffy Blood-Group System / genetics*
  • Female
  • Gene Expression Profiling / statistics & numerical data
  • Genetic Profile
  • Genome-Wide Association Study
  • Humans
  • Leukocyte Count
  • Male
  • Neutropenia* / diagnosis
  • Neutropenia* / ethnology
  • Neutropenia* / genetics
  • Polymorphism, Single Nucleotide
  • Receptors, Cell Surface / genetics*
  • United States / epidemiology
  • Unnecessary Procedures / methods
  • Unnecessary Procedures / statistics & numerical data

Substances

  • ACKR1 protein, human
  • Duffy Blood-Group System
  • Receptors, Cell Surface