Vitamin D Receptor Polymorphisms are Associated with Baseline Muscle Strength and Response to Strength Training

Background: VDR polymorphisms are associated with performance outcomes including hand grip strength and quadriceps strength. However, the positive associations identified in several of these these studies have not proven reproducible when evaluated in other cohorts. Objective: Given persistent ambiguity regarding the influence of vitamin D receptor polymorphisms on muscle strength, we chose to evaluate the influence of five previously studied VDR variants (A1012G/ rs4516035, Fok1/ rs2228570, Ddel/ rs3782905, Bsm1/ rs1544410, Taq1/ rs731236) on a broader range of muscular performance measures in two cohorts of young adults. Studying the genetic determinants of muscle strength development may create the potential to predict adults who are more likely to suffer from sarcopenia, an age-related loss in muscle mass and strength that has been associated with loss of independence and poor health outcomes in the elderly. Methods: Two cohorts of young adults, The Functional Single Nucleotide Polymorphism Associated with Human Muscle Size and Strength (FAMuSS) and Assessing Inherited Markers of Metabolic Syndrome in the Young (AIMMY), were genotyped using Illumina Multi-Ethnic Genotyping Arrays (MEGA). All outcomes were adjusted for age and tested in gender-specific cohorts using both additive and dominant genetic models. ANCOVA models were used to analyze the relationship between genotype and several muscle strength phenotypes. Results: In FAMuSS, males with at least one copy of the rare allele of rs2228570 (Fok1) had significantly greater baseline MVIC strength in the exercised arm (p=0.049), but lesser 12-week change in whole muscle volume of the exercised arm (p=0.034) than those with only the common allele. In AIMMY, Caucasian females with at least one copy of the rare allele of rs2228570 (Fok1) showed greater right hand grip strength (p=0.035), while African American females with the rare allele of rs4516035 (A1012G) (N=11) showed greater left hand grip strength (p=0.046). The Fok1 site thymine/cytosine polymorphism alters an ACG codon, resulting in an earlier upstream start codon that affects transcriptional activity. Discussion: The current study extends our knowledge of VDR variants influencing muscular strength by including an African American cohort, and exploring additional muscle strength phenotypes: biceps size and maximum voluntary isometric contraction (MVIC), and the functional response to a 12-week strength training program. This validation study solidifies the connection between VDR polymorphisms and muscle strength by extending the relationship to biceps strength and response to a 12-week strength training program