Bertoccini Laura, Bailetti Diego, 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
Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
Unit of Biostatistics, IRCSS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
Oncotarget. 2018 Oct 9;9(79):34911-34918. doi: 10.18632/oncotarget.26178.
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 ( rs12785878, rs10741657, 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 ( = 1 x 10-4) and rs4588 ( = 1 x 10-6) but not rs10741657 ( = 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 ( = 1.1 x 10-11) and insufficiency (<30 ng/ml) (OR, 95%CI = 1.28, 1.16-1.41, = 1.1 x 10-7). In conclusion, DHCR7 rs12785878 and 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.
2型糖尿病（T2D）患者的死亡率会升高。维生素D水平低与T2D患者死亡风险增加有关。在普通人群中，影响维生素D代谢的基因变异（rs12785878、rs10741657、rs4588）与血清维生素D有关。我们在来自“萨皮恩扎大学糖尿病死亡率和发病率事件率（SUMMER）研究”的2163例T2D患者中研究了这些变异与血清维生素D的关联。血清维生素D的测量进行了集中化处理。通过Eco™实时PCR获得基因型。数据针对性别、年龄、体重指数、糖化血红蛋白、T2D治疗和采样季节进行了调整。DHCR7基因的rs12785878（P = 1×10⁻⁴）和rs4588（P = 1×10⁻⁶）与维生素D水平显著相关，但rs10741657（P = 0.31）并非如此。加权基因型风险评分（GRS）的一个单位与维生素D水平（P = 1.1×10⁻¹¹）和维生素D不足（<30 ng/ml）（比值比，95%置信区间 = 1.28，1.16 - 1.41，P = 1.1×10⁻⁷）密切相关。总之，DHCR7基因的rs12785878和rs4588与维生素D水平显著相关，但CYP2R1基因的rs10741657并非如此。当将这3个变异一起视为GRS时，观察到与维生素D水平和维生素D不足存在强烈关联，从而提供了有力证据表明参与维生素D代谢的基因可调节T2D患者的血清维生素D水平。
