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Variants of the IL‐10 gene associate with muscle strength in elderly from rural Africa: a candidate gene study
Authors:David van Bodegom  Maris Kuningas  Pieternella E. Slagboom  Johannes J. Meij  Andrea B. Maier  Rudi G. J. Westendorp
Affiliation:1. Department of Gerontology and Geriatrics, Leiden University Medical Center, , Leiden, 2333 ZA The Netherlands;2. Leyden Academy on Vitality and Ageing, , Leiden, 2333 AA The Netherlands;3. Department of Epidemiology, Erasmus Medical Center, , Rotterdam, 3015 GE The Netherlands;4. Department of Medical Statistics, Molecular Epidemiology, Leiden University Medical Center, , Leiden, 2333 ZA The Netherlands;5. Department of Medical Innovation, Amphia Hospitals, , Breda, 4818 CK The Netherlands;6. Section of Gerontology and Geriatrics, Department of Internal Medicine, VU University Medical Center, , Amsterdam, 1081 HV The Netherlands
Abstract:Recently, it has been shown that the capacity of the innate immune system to produce cytokines relates to skeletal muscle mass and strength in older persons. The interleukin‐10 (IL‐10) gene regulates the production capacities of IL‐10 and tumour necrosis factor‐α (TNF‐α). In rural Ghana, IL‐10 gene variants associated with different production capacities of IL‐10 and TNF‐α are enriched compared with Caucasian populations. In this setting, we explored the association between these gene variants and muscle strength. Among 554 Ghanaians aged 50 years and older, we determined 20 single nucleotide polymorphisms in the IL‐10 gene, production capacities of IL‐10 and TNF‐α in whole blood upon stimulation with lipopolysaccharide (LPS) and handgrip strength as a proxy for skeletal muscle strength. We distinguished pro‐inflammatory haplotypes associated with low IL‐10 production capacity and anti‐inflammatory haplotypes with high IL‐10 production capacity. We found that distinct haplotypes of the IL‐10 gene associated with handgrip strength. A pro‐inflammatory haplotype with a population frequency of 43.2% was associated with higher handgrip strength (= 0.015). An anti‐inflammatory haplotype with a population frequency of 7.9% was associated with lower handgrip strength (= 0.006). In conclusion, variants of the IL‐10 gene contributing to a pro‐inflammatory cytokine response associate with higher muscle strength, whereas those with anti‐inflammatory response associate with lower muscle strength. Future research needs to elucidate whether these effects of variation in the IL‐10 gene are exerted directly through its role in the repair of muscle tissue or indirectly through its role in the defence against infectious diseases.
Keywords:Africa  cytokine production  IL‐10 gene  innate immunity  muscle strength
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