Association between Polymorphisms in Vitamin D Pathway-Related Genes, Vitamin D Status, Muscle Mass and Function: A Systematic Review

Abstract

An association between vitamin D level and muscle-related traits has been frequently reported. Vitamin D level is dependent on various factors such as sunlight exposure and nutrition. But also on genetic factors. We, therefore, hypothesize that single nucleotide polymorphisms (SNPs) within the vitamin D pathway-related genes could contribute to muscle mass and function via an impact on vitamin D level. However, the integration of studies investigating these issues is still missing. Therefore, this review aimed to systematically identify and summarize the available evidence on the association between SNPs within vitamin D pathway-related genes and vitamin D status as well as various muscle traits in healthy adults. The review has been registered on PROSPERO and was conducted following PRISMA guidelines. In total, 77 studies investigating 497 SNPs in 13 different genes were included, with significant associations being reported for 59 different SNPs. Variations in GC, CYP2R1, VDR, and CYP24A1 genes were reported most frequently, whereby especially SNPs in the GC (rs2282679, rs4588, rs1155563, rs7041) and CYP2R1 genes (rs10741657, rs10766197, rs2060793) were confirmed to be associated with vitamin D level in more than 50% of the respective studies. Various muscle traits have been investigated only in relation to four different vitamin D receptor (VDR) polymorphisms (rs7975232, rs2228570, rs1544410, and rs731236). Interestingly, all of them showed only very low confirmation rates (6–17% of the studies). In conclusion, this systematic review presents one of the most comprehensive updates of the association of SNPs in vitamin D pathway-related genes with vitamin D status and muscle traits in healthy adults. It might be used for selecting candidate SNPs for further studies, but also for personalized strategies in identifying individuals at risk for vitamin D deficiency and eventually for determining a potential response to vitamin D supplementation.

Haplotypes in the GC, CYP2R1 and CYP24A1 Genes and Biomarkers of Bone Mineral Metabolism in Older Adults

“…Recently, a systematic review of polymorphisms in vitamin D pathway-related genes and vitamin D status showed the highest confirmation rates were found for SNPs in the GC gene rs2282679 (association to vitamin D status confirmed in 77% of the studies); rs4588 (confirmed in 73% of the studies) and in the CYP2R1 gene rs10741657 (confirmed in 66% of the studies). On the other hand, as further frequently studied SNPs located in the CYP24A1 gene, rs6013897 SNP was confirmed in 17% of studies [49]. The aforementioned results are in agreement with the differences we have found in our study.…”

Clinical Practice in the Prevention, Diagnosis and Treatment of Vitamin D Deficiency: A Central and Eastern European Expert Consensus Statement

“…Being aware that it is an individual continuum from vitamin D deficiency to a sufficient and optimal vitamin D status, as well as to vitamin D toxicity, we suggest a classification system, as indicated in Table 4 . It should be kept in mind that such a general classification of vitamin D status cannot take into account variations in the individual sensitivity to vitamin D effects that may be due to genetic polymorphisms, epigenetic or nutritional factors (e.g., magnesium status), as well as co-morbidities or medications [ 48 , 49 , 50 , 51 , 52 ].…”

Critical Appraisal of Large Vitamin D Randomized Controlled Trials

“…and may thus modulate the individual sensitivity to effects of vitamin D supplementation [92,93]. Similarly, genetic polymorphisms related to VDR signaling or vitamin D metabolism may also contribute to individual differences in the response to vitamin D supplementation [94]. Overall, future vitamin D research should put more emphasis on a personalized approach.…”