Background: Vitamin D-deficiency or insufficiency (i.e., low serum 25-hydroxyvitamin D, 25D) is associated with skeletal muscle myopathy [1,2] in addition to being linked to impaired sports performance. We recently identified a molecular role for the 1,25-dihydroxyvitamin D (1,25D) system in muscle mass regulation, via the Vitamin D Receptor (VDR). Yet, an understanding of the role of the vitamin D-axis in muscle health is unresolved. Reflecting this, the impact of vitamin D-related genetic variation in relation to skeletal muscle health and performance is unclear. We therefore aimed i) to review studies relating to muscle function and single nucleotide polymorphisms (SNPs) in vitamin D-axis genes, and ii) to investigate relationships between VDR SNPs and biochemical and physiological parameters of masters athletes (MA) [3].
 
Methods: Firstly, A systematic review of articles published between January 2000 and July 2021 was performed by searching PubMed, EMBASE and Web of Science for articles investigating associations between functionally relevant variants of genes within the vitamin D pathway and skeletal muscle function outcomes. Human research articles were included regardless of language or article type; article quality/risk of bias was assessed by using the Quality of Genetic Association Studies (Q-Genie) tool. Secondly, an elite master athlete (MA) cohort (N = 48) and age-matched controls (N = 48) were genotyped for 6 distinct VDR SNPs (BsmI, FokI, ApaI, Cdx2, TaqI, and A1012G) using the tetra-primer amplification refractory mutation system (tetra-ARMS) and TaqMan allelic discrimination assays. Physiological parameters in cohorts included body composition, handgrip strength (HGS) and muscle function; biochemical markers were examined in controls only [3]. Statistical analysis was performed by one-way ANOVA with Tukey’s post-hoc test for multiple comparisons (significance P<0.05).
 
Results: Twenty-one articles were included in the systematic review with 81% solely including participants aged ≥50 y, and of the 9 studies that included individuals of ethnic minorities, only 2 included black participants. A total of 20 different VDR SNPs were investigated in relation to muscle function, with multiple studies identifying associations with muscle physiology and BsmI, FokI, ApaI, and A1012G. Notably, A1012G was associated with improved handgrip strength, whereas results for other SNPs were conspicuously variable between studies. In agreement, MA carrying A1012G displayed greater HGS (P = 0.0455), whilst controls carrying this SNP also displayed higher jump power (P = 0.0132). Interestingly, controls homozygous for A1012G or Cdx2 had significantly higher levels of serum sex hormone binding globulin (SHBG) (P = 0.048 and 0.0227, respectively).  
 
Conclusions: To conclude, our initial systematic review exemplifies that research into the impact of genetic polymorphisms of vitamin D-related genes in relation to muscle health and function is largely restricted to the VDR gene. In addition, our findings from genetic association analyses in elite MA validate previous findings of associations between A1012G and improved muscle/physical function while also suggesting a putative link to athletic prowess. Finally, we provide evidence of potential novel associations between the vitamin D system and sex hormones warranting further study.