PMID- 30772894
OWN - NLM
STAT- MEDLINE
DCOM- 20200924
LR  - 20240328
IS  - 1758-535X (Electronic)
IS  - 1079-5006 (Print)
IS  - 1079-5006 (Linking)
VI  - 75
IP  - 2
DP  - 2020 Jan 20
TI  - Sarcopenia and Variation in the Human Leukocyte Antigen Complex.
PG  - 301-308
LID - 10.1093/gerona/glz042 [doi]
AB  - BACKGROUND: Aging is characterized by chronic inflammation plus loss of muscle 
      mass and strength, termed sarcopenia. Human leukocyte antigen (HLA) types are 
      drivers of autoimmune disease, although with limited penetrance. We tested 
      whether autoimmune diagnoses are associated with sarcopenia, and whether HLA 
      types and related genetic variants are associated with sarcopenia in autoimmune 
      disease-free older people. METHODS: Data were collected from 181,301 UK Biobank 
      European descent volunteers aged 60-70 with measured hand grip strength and 
      impedance. Logistic regression analysis estimated HLA type and sarcopenia 
      associations, adjusted for confounders and multiple testing. RESULTS: Having any 
      autoimmune diagnosis was associated with sarcopenia (odds ratio [OR] 1.83, 95% 
      confidence interval (CI) 1.74-1.92, p = 4.0*10-125). After excluding autoimmune 
      diagnoses, 6 of 100 HLA types (allele frequency >1%) were associated with 
      sarcopenia (low grip strength and muscle mass). Having two HLA-DQA1*03:01 alleles 
      increased odds of sarcopenia by 19.3% (OR 1.19, CI 1.09-1.29, p = 2.84*10-5), 
      compared to no alleles. Having >/=6 of the 12 HLA alleles increased sarcopenia odds 
      by 23% (OR 1.23, CI 1.12-1.35, p = 7.28*10-6). Of 658 HLA region non-coding 
      genetic variants previously implicated in disease, 4 were associated with 
      sarcopenia, including rs41268896 and rs29268645 (OR 1.08, CI 1.05-1.11, p = 
      1.06*10-8 and 1.07, CI 1.04-1.09, p = 1.5*10-6, respectively). Some HLA 
      associations with sarcopenia were greater in female participants. CONCLUSION: 
      Autoimmune diagnoses are strongly associated with sarcopenia in 60- to 70-year 
      olds. Variation in specific HLA types and non-coding single nucleotide 
      polymorphisms is also associated with sarcopenia in older carriers free of 
      diagnosed autoimmune diseases. Patients with sarcopenia might benefit from 
      targeted treatment of autoimmune processes.
CI  - (c) The Author(s) 2019. Published by Oxford University Press on behalf of The 
      Gerontological Society of America.
FAU - Jones, Garan
AU  - Jones G
AD  - Epidemiology and Public Health Group, University of Exeter Medical School.
FAU - Pilling, Luke C
AU  - Pilling LC
AD  - Epidemiology and Public Health Group, University of Exeter Medical School.
FAU - Kuo, Chia-Ling
AU  - Kuo CL
AD  - Biostatistics Center, CT Institute for Clinical &Translational Science, 
      Department of Community Medicine and Health Care, University of Connecticut 
      Health Center, Farmington.
AD  - Center on Aging, University of Connecticut Health Center, Farmington.
FAU - Kuchel, George
AU  - Kuchel G
AD  - Center on Aging, University of Connecticut Health Center, Farmington.
FAU - Ferrucci, Luigi
AU  - Ferrucci L
AD  - National Institute on Aging, Baltimore, Maryland.
FAU - Melzer, David
AU  - Melzer D
AD  - Epidemiology and Public Health Group, University of Exeter Medical School.
AD  - Center on Aging, University of Connecticut Health Center, Farmington.
LA  - eng
GR  - MC_PC_17228/MRC_/Medical Research Council/United Kingdom
GR  - MC_QA137853/MRC_/Medical Research Council/United Kingdom
GR  - MR/M023095/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Gerontol A Biol Sci Med Sci
JT  - The journals of gerontology. Series A, Biological sciences and medical sciences
JID - 9502837
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Aged
MH  - Autoimmune Diseases/*genetics/*immunology/physiopathology
MH  - Female
MH  - Genome-Wide Association Study
MH  - Genotype
MH  - HLA Antigens/*immunology
MH  - Hand Strength
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Phenotype
MH  - Polymorphism, Single Nucleotide
MH  - Sarcopenia/*genetics/*immunology/physiopathology
MH  - Surveys and Questionnaires
MH  - United Kingdom
PMC - PMC7176057
OTO - NOTNLM
OT  - Autoimmune
OT  - Inflammation
OT  - Muscle
OT  - UK Biobank
EDAT- 2019/02/18 06:00
MHDA- 2020/09/25 06:00
PMCR- 2019/02/17
CRDT- 2019/02/18 06:00
PHST- 2018/06/26 00:00 [received]
PHST- 2019/02/18 06:00 [pubmed]
PHST- 2020/09/25 06:00 [medline]
PHST- 2019/02/18 06:00 [entrez]
PHST- 2019/02/17 00:00 [pmc-release]
AID - 5321878 [pii]
AID - glz042 [pii]
AID - 10.1093/gerona/glz042 [doi]
PST - ppublish
SO  - J Gerontol A Biol Sci Med Sci. 2020 Jan 20;75(2):301-308. doi: 
      10.1093/gerona/glz042.