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Association between CUBN gene variants, type 2 diabetes and vitamin D concentrations in an elderly Greek population.
The Journal of Steroid Biochemistry and Molecular Biology ( IF 2.7 ) Pub Date : 2019-11-23 , DOI: 10.1016/j.jsbmb.2019.105549
Xanthippi Tsekmekidou 1 , Fotis Tsetsos 2 , Theocharis Koufakis 1 , Spyridon N Karras 1 , Marianthi Georgitsi 3 , Nikolaos Papanas 4 , Dimitrios Papazoglou 4 , Athanasios Roumeliotis 5 , Stylianos Panagoutsos 5 , Elias Thodis 5 , Marios Theodoridis 5 , Ploumis Pasadakis 5 , Eustratios Maltezos 4 , Peristera Paschou 2 , Kalliopi Kotsa 1
Affiliation  

Accumulating evidence suggests a potential implication of vitamin D biological network in the pathogenesis of diabetes mellitus. The megalin-cubilin endocytotic system constitutes a key transport structure, with a modulating role in vitamin D metabolism. We aimed to assess the contribution of variants in the CUBN gene to the genetic risk of Type 2 Diabetes Mellitus (T2DM). 95 polymorphisms within CUBN were genotyped in 716 patients with T2DM and 542 controls of Greek origin. Samples were analyzed on Illumina Human PsychArray. Permutation test analysis was implemented to determine statistical significance. Twenty-five-hydroxy-vitamin-D [25(OH)D)] levels were measured in a sub-group of participants (n = 276). Permutation analysis associated rs11254375_G/T (pemp = 0.00049, OR = 1.482), rs6602175_G/T (pemp = 0.016, OR = 0.822), rs1801224_G/T (pemp = 0.025, OR = 0.830), rs4366393_A/G (pemp = 0.028, OR = 0.829) and rs7071576_A/G (pemp = 0.04, OR = 1.219) with T2DM. Mean 25(OH)D concentrations were significantly lower in patients with T2DM compared to controls (16.70 ± 6.69 ng/ml vs 18.51 ± 6.71 ng/ml, p < 0.001), although both groups were vitamin D deficient. In a further quantitative analysis, rs41301097 was strongly associated with higher 25(OH)D concentrations (p = 5.233e-6, beta = 15.95). Our results indicate a potential role of CUBN gene in T2DM genetic susceptibility in the Greek population. These findings may also denote an indirect effect of vitamin D metabolism dysregulation on the pathogenesis of T2DM. Further studies are required to replicate our findings and clarify the complex underlying mechanisms.

中文翻译:

希腊老年人群中CUBN基因变异,2型糖尿病和维生素D浓度之间的关联。

越来越多的证据表明,维生素D生物网络可能在糖尿病的发病机理中具有潜在的意义。megalin-cubilin内吞系统构成关键的转运结构,在维生素D代谢中起调节作用。我们旨在评估CUBN基因变异对2型糖尿病(T2DM)遗传风险的贡献。在716名T2DM患者和542名希腊裔对照中对CUBN中的95个多态性进行了基因分型。在Illumina Human PsychArray上分析样品。进行置换检验分析以确定统计学显着性。在参与者的亚组中测量了25个羟基维生素D [25(OH)D](n = 276)。与rs11254375_G / T(pemp = 0.00049,OR = 1.482),rs6602175_G / T(pemp = 0.016,OR = 0.822),rs1801224_G / T(pemp = 0)相关的排列分析。025,OR = 0.830),带有T2DM的rs4366393_A / G(pemp = 0.028,OR = 0.829)和rs7071576_A / G(pemp = 0.04,OR = 1.219)。T2DM患者的平均25(OH)D浓度显着低于对照组(16.70±6.69 ng / ml与18.51±6.71 ng / ml,p <0.001),尽管两组均缺乏维生素D。在进一步的定量分析中,rs41301097与较高的25(OH)D浓度密切相关(p = 5.233e-6,β= 15.95)。我们的结果表明CUBN基因在希腊人群中T2DM遗传易感性中的潜在作用。这些发现也可能表明维生素D代谢失调对T2DM发病机制的间接影响。需要进一步的研究来复制我们的发现并阐明复杂的潜在机制。829)和带有T2DM的rs7071576_A / G(pemp = 0.04,OR = 1.219)。T2DM患者的平均25(OH)D浓度显着低于对照组(16.70±6.69 ng / ml与18.51±6.71 ng / ml,p <0.001),尽管两组均缺乏维生素D。在进一步的定量分析中,rs41301097与较高的25(OH)D浓度密切相关(p = 5.233e-6,β= 15.95)。我们的结果表明CUBN基因在希腊人群中T2DM遗传易感性中的潜在作用。这些发现也可能表明维生素D代谢失调对T2DM发病机制的间接影响。需要进一步的研究来复制我们的发现并阐明复杂的潜在机制。829)和带有T2DM的rs7071576_A / G(pemp = 0.04,OR = 1.219)。T2DM患者的平均25(OH)D浓度显着低于对照组(16.70±6.69 ng / ml与18.51±6.71 ng / ml,p <0.001),尽管两组均缺乏维生素D。在进一步的定量分析中,rs41301097与较高的25(OH)D浓度密切相关(p = 5.233e-6,β= 15.95)。我们的结果表明CUBN基因在希腊人群中T2DM遗传易感性中的潜在作用。这些发现也可能表明维生素D代谢失调对T2DM发病机制的间接影响。需要进一步的研究来复制我们的发现并阐明复杂的潜在机制。69 ng / ml和18.51±6.71 ng / ml,p <0.001),尽管两组均缺乏维生素D。在进一步的定量分析中,rs41301097与较高的25(OH)D浓度密切相关(p = 5.233e-6,β= 15.95)。我们的结果表明CUBN基因在希腊人群中T2DM遗传易感性中的潜在作用。这些发现也可能表明维生素D代谢失调对T2DM发病机制的间接影响。需要进一步的研究来复制我们的发现并阐明复杂的潜在机制。69 ng / ml和18.51±6.71 ng / ml,p <0.001),尽管两组均缺乏维生素D。在进一步的定量分析中,rs41301097与较高的25(OH)D浓度密切相关(p = 5.233e-6,β= 15.95)。我们的结果表明CUBN基因在希腊人群中T2DM遗传易感性中的潜在作用。这些发现也可能表明维生素D代谢失调对T2DM发病机制的间接影响。需要进一步的研究来复制我们的发现并阐明复杂的潜在机制。我们的结果表明CUBN基因在希腊人群中T2DM遗传易感性中的潜在作用。这些发现也可能表明维生素D代谢失调对T2DM发病机制的间接影响。需要进一步的研究来复制我们的发现并阐明复杂的潜在机制。我们的结果表明CUBN基因在希腊人群中T2DM遗传易感性中的潜在作用。这些发现也可能表明维生素D代谢失调对T2DM发病机制的间接影响。需要进一步的研究来复制我们的发现并阐明复杂的潜在机制。
更新日期:2019-11-26
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