Mortality rate is increased in type 2 diabetes (T2D). Low vitamin D levels are associated with increased mortality risk in T2D. In the general population, genetic variants affecting vitamin D metabolism (DHCR7 rs12785878, CYP2R1 rs10741657, GC rs4588) have been associated with serum vitamin D. We studied the association of these variants with serum vitamin D in 2163 patients with T2D from the "Sapienza University Mortality and Morbidity Event Rate (SUMMER) study in diabetes". Measurements of serum vitamin D were centralised. Genotypes were obtained by EcoTM Real-Time PCR. Data were adjusted for gender, age, BMI, HbA1c, T2D therapy and sampling season. DHCR7 rs12785878 (p = 1 × 10-4) and GC rs4588 (p = 1 × 10-6) but not CYP2R1 rs10741657 (p = 0.31) were significantly associated with vitamin D levels. One unit of a weighted genotype risk score (GRS) was strongly associated with vitamin D levels (p = 1.1 × 10-11) and insufficiency (<30 ng/ml) (OR, 95%CI = 1.28, 1.16-1.41, p = 1.1 × 10-7). In conclusion, DHCR7 rs12785878 and GC rs4588, but not CYP2R1 rs10741657, are significantly associated with vitamin D levels. When the 3 variants were considered together as GRS, a strong association with vitamin D levels and vitamin D insufficiency was observed, thus providing robust evidence that genes involved in vitamin D metabolism modulate serum vitamin D in T2D.
Variability in genes regulating Vitamin D metabolism is associated with Vitamin D levels in type 2 diabetes / Bertoccini, L., Bailetti, D., Buzzetti, R., Cavallo, M.G., Copetti, M., Cossu, E., D'Angelo, P., De Cosmo, S., Di Mauro, L., Leonetti, F., Morano, S., Morviducci, L., Napoli, N., Prudente, S., Pugliese, G., Trischitta, V., Baroni, M.G., Alessi, E., Bagella, F., Barchetta, I., et al.. - In: ONCOTARGET. - ISSN 1949-2553. - 9:79(2018), pp. 34911-34918. [10.18632/oncotarget.26178]
Variability in genes regulating Vitamin D metabolism is associated with Vitamin D levels in type 2 diabetes
Scarale M. G.;
2018-01-01
Abstract
Mortality rate is increased in type 2 diabetes (T2D). Low vitamin D levels are associated with increased mortality risk in T2D. In the general population, genetic variants affecting vitamin D metabolism (DHCR7 rs12785878, CYP2R1 rs10741657, GC rs4588) have been associated with serum vitamin D. We studied the association of these variants with serum vitamin D in 2163 patients with T2D from the "Sapienza University Mortality and Morbidity Event Rate (SUMMER) study in diabetes". Measurements of serum vitamin D were centralised. Genotypes were obtained by EcoTM Real-Time PCR. Data were adjusted for gender, age, BMI, HbA1c, T2D therapy and sampling season. DHCR7 rs12785878 (p = 1 × 10-4) and GC rs4588 (p = 1 × 10-6) but not CYP2R1 rs10741657 (p = 0.31) were significantly associated with vitamin D levels. One unit of a weighted genotype risk score (GRS) was strongly associated with vitamin D levels (p = 1.1 × 10-11) and insufficiency (<30 ng/ml) (OR, 95%CI = 1.28, 1.16-1.41, p = 1.1 × 10-7). In conclusion, DHCR7 rs12785878 and GC rs4588, but not CYP2R1 rs10741657, are significantly associated with vitamin D levels. When the 3 variants were considered together as GRS, a strong association with vitamin D levels and vitamin D insufficiency was observed, thus providing robust evidence that genes involved in vitamin D metabolism modulate serum vitamin D in T2D.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
