Variability in genes regulating Vitamin D metabolism is associated with Vitamin D levels in type 2 diabetes

Laura Bertoccini, Diego Bailetti, Raffaella Buzzetti, Maria Gisella Cavallo, Massimiliano Copetti, Efisio Cossu, Paola D'Angelo, Salvatore De Cosmo, Lazzaro Di Mauro, Frida Leonetti, Susanna Morano, Lelio Morviducci, Nicola Napoli, Sabrina Prudente, Giuseppe Pugliese, Vincenzo Trischitta, Marco Giorgio Baroni

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)34911-34918
Number of pages8
Issue number79
Publication statusPublished - Jan 1 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

ASJC Scopus subject areas

  • Oncology


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