The associations of vitamin D and metal exposures with inflammation, autoimmunity, and blood pressure

1,25(OH)2D, the biologically active form of vitamin D, is not commonly measured, as it is tightly regulated and does not change with supplementation or sun exposure unlike 25(OH)D. Prior studies suggest that exposure to metals may inhibit production of 1,25(OH)2D from 25(OH)D. Epidemiological studies have linked higher 25(OH)D with lower inflammation, while not measuring 1,25(OH)2D. In addition, while many studies suggest opposing effects of lead (Pb) and 25(OH)D on blood pressure, no study has looked at them together. Finally, while several metals are thought to increase inflammation, only mercury (Hg) has been studied as a risk factor for autoimmunity. The goal of this dissertation was to expand upon previous studies suggesting inhibition of production of 1,25(OH)2D with exposure to metals, to expand upon previous research suggesting an inverse association between 25(OH)D and inflammation by including 1,25(OH)2D; to see if 25(OH)D would attenuate the association between Pb and increased blood pressure; and to see if metals other than Hg increase risk for autoimmunity. We first conducted an analysis of metals with 25(OH)D and 1,25(OH)2D. The study population was a cohort of adolescents aged 12-15 residing in Torreon, a city in Mexico home to a large Pb smelter. We found no evidence that any metal was inhibiting production of 1,25(OH)2D, and instead found that higher exposures to uranium (U) and arsenic (As) were associated with increased levels of 1,25(OH)2D. Second, we described the associations of 25(OH)D and 1,25(OH)2D with inflammation, using the study population from Torreon. 25(OH)D was positively associated with IL-1β and P-selectin, and inversely associated with ICAM and VCAM. 1,25(OH)2D was positively associated with ICAM, VCAM, and TNF-α. Third, we used logistic regression to analyze metals as a risk factor for autoimmunity measured by anti-nuclear antibodies (ANA). We found no significant associations between ANA and any of the eight metals measured, suggesting that increased risk of autoimmunity may be unique to Hg. Finally, we used the NHANES dataset to assess 25(OH)D as an effect modifier of Pb and blood pressure. While we did find a significant interaction of 25(OH)D and Pb, the interaction term was no longer significant after adjusting for socioeconomic status and smoking