Human Genetics

, Volume 132, Issue 6, pp 619–627

Genome-wide association study identified the human leukocyte antigen region as a novel locus for plasma beta-2 microglobulin

  • Adrienne Tin
  • Brad C. Astor
  • Eric Boerwinkle
  • Ron C. Hoogeveen
  • Josef Coresh
  • Wen Hong Linda Kao
Original Investigation

Abstract

Beta-2 microglobulin (B2M) is a component of the major histocompatibility complex (MHC) class I molecule and has been studied as a biomarker of kidney function, cardiovascular diseases and mortality. Little is known about the genes influencing its levels directly or through glomerular filtration rate (GFR). We conducted a genome-wide association study of plasma B2M levels in 6738 European Americans from the Atherosclerosis Risk in Communities study to identify novel loci for B2M and assessed its association with known estimated GFR (eGFR) loci. We identified 2 genome-wide significant loci. One was in the human leukocyte antigen (HLA) region on chromosome 6 (lowest p value = 1.8 × 10−23 for rs9264638). At this locus, 6 index SNPs accounted for 3.2 % of log(B2M) variance, and their association with B2M could largely be explained by imputed classical alleles of the MHC class I genes: HLA-A, HLA-B, or HLA-C. The index SNPs at this locus were not associated with eGFR based on serum creatinine (eGFRcr). The other locus of B2M was on chromosome 12 (rs3184504 at SH2B3, beta = 0.02, p value = 3.1 × 10−8), which was previously implicated as an eGFR locus. In conclusion, although B2M is known to be a component of MHC class I molecule, the association between HLA class I alleles and plasma B2M levels in a community-based population is novel. The identification of the two novel loci for B2M extends our understanding of its metabolism and informs its use as a kidney filtration biomarker.

Supplementary material

439_2013_1274_MOESM1_ESM.doc (521 kb)
Supplementary material 1 (DOC 521 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Adrienne Tin
    • 1
  • Brad C. Astor
    • 2
  • Eric Boerwinkle
    • 3
  • Ron C. Hoogeveen
    • 4
  • Josef Coresh
    • 5
  • Wen Hong Linda Kao
    • 1
  1. 1.Department of EpidemiologyJohns Hopkins Bloomberg School of Public HealthBaltimoreUSA
  2. 2.Department of Medicine, School of Medicine and Public HealthUniversity of WisconsinMadisonUSA
  3. 3.Human Genetics CenterThe University of Texas Health Science Center at HoustonHoustonUSA
  4. 4.The Margaret M. and Albert B. Alkek Department of Medicine, Division of Atherosclerosis and Vascular MedicineBaylor College of MedicineHoustonUSA
  5. 5.Welch Center for Prevention, Epidemiology and Clinical ResearchThe Johns Hopkins Medical InstitutionsBaltimoreUSA

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