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.; Capoccia, D.; Carletti, S.; Coccia, F.; Conti, F.; D'Onofrio, L.; Filardi, T.; Leanza, G.; Margiotta, G.; Incani, M.; Moretti, C.; Pezzilli, S.; Pibiri, C.; Piscitelli, P.; Scarale, M. G.; Sentinelli, F.; Tavaglione, F.. - 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.
2018
CYP2R1 (Cytochrome P450 Family 2 Subfamily R Member 1)
DHCR7 (7-dehydrocholesterol reductase)
GC (Vitamin D Binding Protein)
Genetic risk score
SUMMER Study in Diabetes
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11768/124677
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