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

TitleGenome-wide association study identified the human leukocyte antigen region as a novel locus for plasma beta-2 microglobulin.
Publication TypeJournal Article
Year of Publication2013
AuthorsTin A, Astor BC, Boerwinkle E, Hoogeveen RC, Coresh JJ
Secondary AuthorsKao W H L
JournalHum Genet
Volume132
Issue6
Pagination619-27
Date Published2013 Jun
ISSN1432-1203
Keywordsbeta 2-Microglobulin, Chromosomes, Human, Pair 12, Chromosomes, Human, Pair 6, Creatinine, Female, Genetic Loci, Genome-Wide Association Study, Glomerular Filtration Rate, HLA Antigens, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide
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.

DOI10.1007/s00439-013-1274-7
Alternate JournalHum Genet
PubMed ID23417110
PubMed Central IDPMC3656139
Grant ListT32 HL007024 / HL / NHLBI NIH HHS / United States