Oncotarget

Research Papers:

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

Laura Bertoccini, Diego Bailetti, SUMMER Study in Diabetes Group, 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 and Marco Giorgio Baroni _

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Oncotarget. 2018; 9:34911-34918. https://doi.org/10.18632/oncotarget.26178

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Abstract

Laura Bertoccini1, Diego Bailetti1, SUMMER Study in Diabetes Group*, Raffaella Buzzetti1, Maria Gisella Cavallo1, Massimiliano Copetti2, Efisio Cossu3, Paola D'Angelo4, Salvatore De Cosmo5, Lazzaro Di Mauro6, Frida Leonetti1, Susanna Morano1, Lelio Morviducci7, Nicola Napoli8, Sabrina Prudente9, Giuseppe Pugliese10, Vincenzo Trischitta1,9 and Marco Giorgio Baroni1

1Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy

2Unit of Biostatistics, IRCSS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy

3Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy

4Unit of Diabetology, Sandro Pertini Hospital, Rome, Italy

5IRCSS Casa Sollievo della Sofferenza, Department of Medicine, San Giovanni Rotondo, Italy

6Laboratory of Clinical Chemistry, IRCSS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy

7Unit of Diabetology, S. Spirito Hospital – AslRM1, Rome, Italy

8Campus Biomedico University, Rome, Italy

9IRCCS Casa Sollievo della Sofferenza, Research Unit of Metabolic and Cardiovascular Diseases, San Giovanni Rotondo, Italy

10Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy

*The Investigators of the “Sapienza University Mortality and Morbidity Event Rate (SUMMER) study in diabetes” Study Group are: Elena Alessi10, Francesco Bagella1, Ilaria Barchetta1, Danila Capoccia1, Silvia Carletti4, Federica Coccia1, Francesco Conti9, Luca D'Onofrio1, Tiziana Filardi1, Giulia Leanza8, Gianluca Margiotta1, Michela Incani3, Chiara Moretti1, Serena Pezzilli9, Carlotta Pibiri1, Pamela Piscitelli5, Maria Giovanna Scarale2, Federica Sentinelli1, Federica Tavaglione1

Correspondence to:

Marco Giorgio Baroni, email: [email protected]

Keywords: genetic risk score; DHCR7 (7-dehydrocholesterol reductase); CYP2R1 (Cytochrome P450 Family 2 Subfamily R Member 1); GC (Vitamin D Binding Protein); SUMMER Study in Diabetes

Received: July 18, 2018     Accepted: September 17, 2018     Published: October 09, 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.


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