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Background  Vitamin D status has been associated with the presence and severity of several premenstrual symptoms (PMSx) in some, but not all studies. Inconsistencies among findings may be explained by unaccounted genetic variation in the vitamin D receptor ( VDR ).    Objective  To determine whether associations between vitamin D status and individual PMSx are influenced by  VDR  genotype.    Methods  Seven hundred sixteen women aged 20-29 years old from the Toronto Nutrigenomics and Health study provided plasma samples and completed a questionnaire on the presence and severity of 15 common PMSx. Plasma 25-hydroxyvitamin D (25(OH)D) concentration was measured and participants were categorized into sufficient (≥ 50 nmol/L) and insufficient (< 50 nmol/L) vitamin D status groups. DNA was obtained from blood samples to genotype for a common  VDR  single nucleotide variant, rs796858. Using logistic regression, odds of experiencing PMSx were compared between vitamin D-sufficient and insufficient women, stratified by genotype.    Results  Among CC homozygotes, insufficient vitamin D status was associated with higher odds of experiencing premenstrual fatigue (OR, 2.53; 95% CI, 1.40, 4.56) and nausea (OR, 2.44; 95% CI, 1.00, 5.95). Among TT homozygotes, insufficient vitamin D status was associated with lower odds of experiencing fatigue (OR, 0.44; 95% CI, 0.20, 0.97) and increased appetite (OR, 0.48; 95% CI, 0.22, 1.04). Insufficient vitamin D status was associated with higher odds of increased appetite in women with the CT genotype (OR, 1.78; 95% CI, 1.03, 3.07).  VDR  genotype modified the association between vitamin D status and the following PMSx: increased appetite (interaction  p  = 0.027), fatigue (interaction  p  = 0.016), and nausea (interaction  p  = 0.039).    Conclusion  We found evidence that  VDR  genotype may modify the association between 25(OH)D and some PMSx. Insufficient 25(OH)D was associated with a higher risk of premenstrual fatigue in those with the CC genotype, but lower risk in those with the TT genotype.    Supplementary Information  The online version contains supplementary material available at 10.1186/s12263-021-00696-2.

Variation in the vitamin D receptor gene, plasma 25-hydroxyvitamin D, and risk of premenstrual symptoms