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™ Real-Time PCR. Data were adjusted for gender, age, BMI, HbA1c, T2D therapy and sampling season. DHCR7 rs12785878 (p = 1 x 10-4) and GC rs4588 (p = 1 x 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 x 10-11) and insufficiency (<30 ng/ml) (OR, 95%CI = 1.28, 1.16-1.41, p = 1.1 x 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, Laura; Bailetti, Diego; SUMMER Study in Diabetes Group (Summer, ; Alessi, Elena; Bagella, FRANCESCO MARIA; Barchetta, Ilaria; Capoccia, Danila; Silvia, Carletti; Coccia, Federica; Conti, Francesco; D'Onofrio, Luca; Filardi, Tiziana; Giulia, Leanza; Gianluca, Margiotta; Incani, Michela; Moretti, Chiara; Pezzilli, Serena; Pibiri, Carlotta; Pamela, Piscitelli; Maria Giovanna Scarale, ; Sentinelli, Federica; Tavaglione, Federica; Buzzetti, Raffaella; Cavallo, Maria Gisella; Copetti, Massimiliano; Cossu, Efisio; D'Angelo, Paola; De Cosmo, Salvatore; Di Mauro, Lazzaro; Leonetti, Frida; Morano, Susanna; Morviducci, Lelio; Napoli, Nicola; Prudente, Sabrina; Pugliese, Giuseppe; Trischitta, Vincenzo; Baroni Marco, Giorgio.. - 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

Bertoccini, Laura;Bailetti, Diego;Elena Alessi;Francesco Bagella;Ilaria Barchetta;Danila Capoccia;Federica Coccia;Francesco Conti;Luca D'Onofrio;Tiziana Filardi;Michela Incani;Chiara Moretti;Serena Pezzilli;Carlotta Pibiri;Federica Sentinelli;Federica Tavaglione);Buzzetti Raffaella;Cavallo, Maria Gisella;Leonetti, Frida;Morano, Susanna;Morviducci, Lelio;Prudente, Sabrina;Pugliese, Giuseppe;Trischitta, Vincenzo;Baroni Marco Giorgio.
2018

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 Eco™ Real-Time PCR. Data were adjusted for gender, age, BMI, HbA1c, T2D therapy and sampling season. DHCR7 rs12785878 (p = 1 x 10-4) and GC rs4588 (p = 1 x 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 x 10-11) and insufficiency (<30 ng/ml) (OR, 95%CI = 1.28, 1.16-1.41, p = 1.1 x 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.
CYP2R1 (Cytochrome P450 Family 2 Subfamily R Member 1); DHCR7 (7-dehydrocholesterol reductase); GC (Vitamin D Binding Protein); SUMMER Study in Diabetes; genetic risk score
01 Pubblicazione su rivista::01a Articolo in rivista
Variability in genes regulating vitamin D metabolism is associated with vitamin D levels in type 2 diabetes / Bertoccini, Laura; Bailetti, Diego; SUMMER Study in Diabetes Group (Summer, ; Alessi, Elena; Bagella, FRANCESCO MARIA; Barchetta, Ilaria; Capoccia, Danila; Silvia, Carletti; Coccia, Federica; Conti, Francesco; D'Onofrio, Luca; Filardi, Tiziana; Giulia, Leanza; Gianluca, Margiotta; Incani, Michela; Moretti, Chiara; Pezzilli, Serena; Pibiri, Carlotta; Pamela, Piscitelli; Maria Giovanna Scarale, ; Sentinelli, Federica; Tavaglione, Federica; Buzzetti, Raffaella; Cavallo, Maria Gisella; Copetti, Massimiliano; Cossu, Efisio; D'Angelo, Paola; De Cosmo, Salvatore; Di Mauro, Lazzaro; Leonetti, Frida; Morano, Susanna; Morviducci, Lelio; Napoli, Nicola; Prudente, Sabrina; Pugliese, Giuseppe; Trischitta, Vincenzo; Baroni Marco, Giorgio.. - In: ONCOTARGET. - ISSN 1949-2553. - 9:79(2018), pp. 34911-34918. [10.18632/oncotarget.26178]
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