PMID- 23417110
OWN - NLM
STAT- MEDLINE
DCOM- 20130709
LR  - 20211021
IS  - 1432-1203 (Electronic)
IS  - 0340-6717 (Print)
IS  - 0340-6717 (Linking)
VI  - 132
IP  - 6
DP  - 2013 Jun
TI  - Genome-wide association study identified the human leukocyte antigen region as a 
      novel locus for plasma beta-2 microglobulin.
PG  - 619-27
LID - 10.1007/s00439-013-1274-7 [doi]
AB  - 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 x 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 
      x 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.
FAU - Tin, Adrienne
AU  - Tin A
AD  - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 
      Baltimore, MD 21205, USA. atin@jhsph.edu
FAU - Astor, Brad C
AU  - Astor BC
FAU - Boerwinkle, Eric
AU  - Boerwinkle E
FAU - Hoogeveen, Ron C
AU  - Hoogeveen RC
FAU - Coresh, Josef
AU  - Coresh J
FAU - Kao, Wen Hong Linda
AU  - Kao WH
LA  - eng
GR  - T32 HL007024/HL/NHLBI NIH HHS/United States
PT  - Journal Article
DEP - 20130216
PL  - Germany
TA  - Hum Genet
JT  - Human genetics
JID - 7613873
RN  - 0 (HLA Antigens)
RN  - 0 (beta 2-Microglobulin)
RN  - AYI8EX34EU (Creatinine)
SB  - IM
MH  - Chromosomes, Human, Pair 12/genetics
MH  - Chromosomes, Human, Pair 6/genetics
MH  - Creatinine/blood
MH  - Female
MH  - Genetic Loci
MH  - Genome-Wide Association Study
MH  - Glomerular Filtration Rate
MH  - HLA Antigens/*genetics
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Polymorphism, Single Nucleotide
MH  - beta 2-Microglobulin/*genetics/metabolism
PMC - PMC3656139
MID - NIHMS446887
EDAT- 2013/02/19 06:00
MHDA- 2013/07/10 06:00
PMCR- 2014/06/01
CRDT- 2013/02/19 06:00
PHST- 2012/10/07 00:00 [received]
PHST- 2013/02/06 00:00 [accepted]
PHST- 2013/02/19 06:00 [entrez]
PHST- 2013/02/19 06:00 [pubmed]
PHST- 2013/07/10 06:00 [medline]
PHST- 2014/06/01 00:00 [pmc-release]
AID - 10.1007/s00439-013-1274-7 [doi]
PST - ppublish
SO  - Hum Genet. 2013 Jun;132(6):619-27. doi: 10.1007/s00439-013-1274-7. Epub 2013 Feb 
      16.