This thesis investigates the role that serum 25(OH)D and serum 1,25(OH)2D
concentration play in skeletal muscle dysfunction in patients with Chronic Obstructive
Pulmonary Disease (COPD) with reference to clinical impact, potential molecular
mechanisms and genetic influences.
In a large cohort of COPD patients, neither serum 25(OH)D or serum 1,25()H)2D
concentration were found to be associated with any volitional or non-volitional
measures of peripheral or respiratory muscle strength. In a group of age and sex
matched healthy control subjects serum 1,25()H)2D concentration was associated with
muscle strength measures even after correction for potential confounding factors.
Vitamin D status was not associated with quadriceps endurance in either COPD or
control subjects when measured by repetitive magnetic stimulation.
A sub-set of patients underwent a quadriceps muscle biopsy and mRNA levels of
muscle fibre type and myogenic regulatory factors were measured. Serum 25(OH)D
concentration was associated with MyHCIIa mRNA expression in control, but not
COPD, subjects. Myf5 mRNA expression was strongly associated with MHC1
mRNA expression whilst mrf4 mRNA expression was strongly associated with
MyHCIIa mRNA expression in control, but not COPD, subjects.
Genotyping for all subjects included in the study was carried out for certain
polymorphisms that were chosen because they have previously been reported to have
an influence on the renin-angiotensin system in normal subjects, and may thus have
an influence on skeletal muscle strength, or were already associated with muscle
strength. In combination, the ACE I/D polymorphism, the AGT Met235Thr and the
ATR1 A1166C polymorphisms had a significant influence on muscle strength in the
COPD group. In normal subjects, the ACE I/D polymorphism was significantly
associated with serum 25(OH)D concentration, and this association was stronger after
correcting for confounding factors.