The ingestion of excessive amounts of vitamin D<sub>3</sub> (or vitamin D<sub>2</sub>) results in hypercalcemia and hypercalciuria due to the formation of supraphysiological amounts of 25-hydroxyvitamin D [25(OH)D] that bind to the vitamin D receptor, albeit with lower affinity than the active form of the vitamin, 1,25(OH)<sub>2</sub>D, and the formation of 5,6-trans 25(OH)D, which binds to the vitamin D receptor more tightly than 25(OH)D. In patients with granulomatous disease such as sarcoidosis or tuberculosis and tumors such as lymphomas, hypercalcemia occurs as a result of the activity of ectopic 25(OH)D-1-hydroxylase (CYP27B1) expressed in macrophages or tumor cells and the formation of excessive amounts of 1,25(OH)<sub>2</sub>D.
The present authors conclude that in African-Americans, the angiotensin converting enzyme, vitamin D receptor, and tumour necrosis factor-alpha genes are not significant risk factors for sarcoidosis susceptibility.
From these results, we speculate that although the VDR gene polymorphism may affect the serum PTH level, it is not a risk factor for hypercalcemia in sarcoidosis.