title: Fine-mapping of HLA associations with chronic lymphocytic leukemia in US populations.
abstract: Chronic lymphocytic leukemia (CLL) displays remarkable ethnic predisposition for whites, with relative sparing of African-American and Asian populations. In addition, CLL displays among the highest familial predispositions of all hematologic malignancies, yet the genetic basis for these differences is not clearly defined. The highly polymorphic HLA genes of the major histocompatibility complex play a central role in immune surveillance and confer risk for autoimmune and infectious diseases and several different cancers, the role for which in the development of CLL has not been extensively investigated. The National Marrow Donor Program/Be The Match has collected HLA typing from CLL patients in need of allogeneic hematopoietic stem cell transplant and has recruited millions of volunteers to potentially donate hematopoietic stem cells. HLA genotypes for 3491 US white, 397 African-American, and 90 Hispanic CLL patients were compared with 50 000 controls per population from the donor registry. We identified several HLA alleles associated with CLL susceptibility in each population, reconfirming predisposing roles of HLA-A*02:01 and HLA-DRB4*01:01 in whites. Associations for haplotype DRB4*01:01∼DRB1*07:01∼DQB1*03:03 were replicated across all 3 populations. These findings provide a comprehensive assessment of the role of HLA in the development of severe CLL.
authors.affiliation: Bioinformatics Research, National Marrow Donor Program/Be The Match, Minneapolis, MN; and.
authors.forename: Loren
authors.initials: L
authors.lastname: Gragert
authors.affiliation: Bioinformatics Research, National Marrow Donor Program/Be The Match, Minneapolis, MN; and.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Fingerson
authors.affiliation: Bioinformatics Research, National Marrow Donor Program/Be The Match, Minneapolis, MN; and.
authors.forename: Mark
authors.initials: M
authors.lastname: Albrecht
authors.affiliation: Bioinformatics Research, National Marrow Donor Program/Be The Match, Minneapolis, MN; and.
authors.forename: Martin
authors.initials: M
authors.lastname: Maiers
authors.affiliation: Hematologic Oncology and Blood Disorders, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Matt
authors.initials: M
authors.lastname: Kalaycio
authors.affiliation: Hematologic Oncology and Blood Disorders, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Hill
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics; D000368:Aged; D000483:Alleles; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D006239:Haplotypes; D006630:Hispanic or Latino / Q000235:genetics; D006650:Histocompatibility Testing / Q000379:methods*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D014481:United States; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D006680:HLA Antigens