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. 2020 Jan 20;75(2):301-308.
doi: 10.1093/gerona/glz042.

Sarcopenia and Variation in the Human Leukocyte Antigen Complex

Garan Jones  1 , Luke C Pilling  1 , Chia-Ling Kuo  2   3 , George Kuchel  3 , Luigi Ferrucci  4 , David Melzer  1   3
Affiliations

Sarcopenia and Variation in the Human Leukocyte Antigen Complex

Garan Jones et al. J Gerontol A Biol Sci Med Sci. .

Abstract

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.

Keywords: Autoimmune; Inflammation; Muscle; UK Biobank.

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Figures

Figure 1.
Figure 1.
Forest plot of HLA types associated with sarcopenia phenotypes. Note: Logistic regression analysis of 100 HLA types associated with sarcopenia (Benjamini–Hochberg correction for multiple testing applied). HLA types passing the false discovery rate cutoff of 0.05 for each phenotype are marked with asterisks (*). CI = confidence interval; EWGSOP = European Working Group on Sarcopenia in Older People, combined sarcopenia definition: low grip strength and muscle mass; HLA = human leukocyte antigen; OR = odds ratio per allele of HLA type.
See this image and copyright information in PMC

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