TY - JOUR
T1 - Variability in genes regulating Vitamin D metabolism is associated with Vitamin D levels in type 2 diabetes
AU - Bertoccini, Laura
AU - Bailetti, Diego
AU - Buzzetti, Raffaella
AU - Cavallo, Maria Gisella
AU - Copetti, Massimiliano
AU - Cossu, Efisio
AU - D'Angelo, Paola
AU - De Cosmo, Salvatore
AU - Di Mauro, Lazzaro
AU - Leonetti, Frida
AU - Morano, Susanna
AU - Morviducci, Lelio
AU - Napoli, Nicola
AU - Prudente, Sabrina
AU - Pugliese, Giuseppe
AU - Trischitta, Vincenzo
AU - Baroni, Marco Giorgio
PY - 2018/1/1
Y1 - 2018/1/1
N2 -
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 Eco
TM
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.
AB -
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 Eco
TM
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.
KW - CYP2R1 (Cytochrome P450 Family 2 Subfamily R Member 1)
KW - DHCR7 (7-dehydrocholesterol reductase)
KW - GC (Vitamin D Binding Protein)
KW - Genetic risk score
KW - SUMMER Study in Diabetes
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M3 - Article
AN - SCOPUS:85063158482
SN - 1949-2553
VL - 9
SP - 34911
EP - 34918
JO - Oncotarget
JF - Oncotarget
IS - 79
ER -