Genetic variation in the human vitamin D receptor is associated with muscle strength, fat mass and body weight in Swedish women

Abstract

Objective: Bone mineral density (BMD) is under strong genetic control and a number of candidate genes have been associated with BMD. Both muscle strength and body weight are considered to be important predictors of BMD but far less is known about the genes affecting muscle strength and fat mass. The purpose of this study was to investigate the poly adenosine (A) repeat and the BsmI SNP in the vitamin D receptor (VDR) in relation to muscle strength and body composition in healthy women. Design: A population-based study of 175 healthy women aged 20-39 years was used. Methods: The polymorphic regions in the VDR gene (the poly A repeat and the BsmI SNP) were amplified by PCR. Body mass measurements (fat mass, lean mass, body weight and body mass index) and muscle strength (quadriceps, hamstring and grip strength) were evaluated. Results: Individuals with shorter poly A repeat, ss and/or absence of the linked BsmI restriction site (BB) have higher hamstring strength (ss vs LL, P ¼ 0.02), body weight (ss vs LL, P ¼ 0.049) and fat mass (ss vs LL, P ¼ 0.04) compared with women with a longer poly A repeat (LL) and/or the presence of the linked BsmI restriction site (bb). Conclusions: Genetic variation in the VDR is correlated with muscle strength, fat mass and body weight in premenopausal women. Further functional studies on the poly A microsatellite are needed to elucidate whether this is the functionally relevant locus or if the polymorphism is in linkage disequilibrium with a functional variant in a closely situated gene further downstream of the VDR 3 0 UTR.European Journal of Endocrinology 150 323-328

Effect of age, gender and calciotropic hormones on the relationship between vitamin D receptor gene polymorphisms and bone mineral density

“…Such difference, if present, would lead to a difference in functional response of muscle to vitamin D and therefore a difference in lean mass between VDR genotypes. There was no relationship between VDR polymorphisms and lean mass in either gender or age group in this study, similarly to what was found in previous studies (Grundberg et al, 2004;Garnero et al, 2005).…”

“…Some studies assessed the relationship between VDR genotypes and muscle strength and/or lean mass in humans (Guesens et al, 1997;Pottelbergh et al, 2002;Grundberg et al, 2004), and between VDR and PTH levels (McClure et al, 1997;Pottelbergh et al, 2002;Zofkova et al, 2003;Macdonald et al, 2006). The expression of VDR in muscle decreases significantly with aging (Bischoff-Ferrari et al, 2004).…”

Association between VDR and ESR1 gene polymorphisms with bone and obesity phenotypes in Chinese male nuclear families

“…More defined phenotypes have been proposed for studying obesity, such as fat mass, lean mass, and percentage fat mass. Genetic variation in VDR is associated with muscle strength, fat mass, and body weight in Swedish women [3] . Recently, however, Moreno et al [41] failed to find an association between VDR genotypes and haplotypes with fat-free mass in postmenopausal Brazilian women.…”

“…These changes may correspondingly lead to osteoporosis and obesity. Both bone mass and obesity phenotypes are known to be under strong genetic regulation [3,4] . In the past decade, a number of candidate genes have been identified that may contribute to bone mineral density (BMD), but far less is known about genes affecting obesity phenotypes such as lean mass and fat mass [5,6] .…”

“…Indeed, it has been demonstrated that vitamin D stimulates the differentiation of preadipocytes to adipocytes in the OB 17 cell line [9] . Some studies have also suggested that VDR genotype may function as a determinant of body composition [3] . Estrogen receptor alpha (ESR1) is also an important potential candidate gene for osteoporosis, and extensive studies have been performed on the relationship between polymorphisms of this gene and BMD variation.…”