PMID- 31770575 OWN - NLM STAT- MEDLINE DCOM- 20200812 LR - 20200812 IS - 1879-1220 (Electronic) IS - 0960-0760 (Linking) VI - 198 DP - 2020 Apr TI - Association between CUBN gene variants, type 2 diabetes and vitamin D concentrations in an elderly Greek population. PG - 105549 LID - S0960-0760(19)30468-6 [pii] LID - 10.1016/j.jsbmb.2019.105549 [doi] AB - 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 (p(emp) = 0.00049, OR = 1.482), rs6602175_G/T (p(emp) = 0.016, OR = 0.822), rs1801224_G/T (p(emp) = 0.025, OR = 0.830), rs4366393_A/G (p(emp) = 0.028, OR = 0.829) and rs7071576_A/G (p(emp) = 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. CI - Copyright (c) 2019 Elsevier Ltd. All rights reserved. FAU - Tsekmekidou, Xanthippi AU - Tsekmekidou X AD - Division of Endocrinology and Metabolism and Diabetes Center, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki, Greece. FAU - Tsetsos, Fotis AU - Tsetsos F AD - Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis, Greece. FAU - Koufakis, Theocharis AU - Koufakis T AD - Division of Endocrinology and Metabolism and Diabetes Center, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki, Greece. FAU - Karras, Spyridon N AU - Karras SN AD - Division of Endocrinology and Metabolism and Diabetes Center, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki, Greece. FAU - Georgitsi, Marianthi AU - Georgitsi M AD - Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis, Greece; Laboratory of General Biology-Genetics, Department of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Papanas, Nikolaos AU - Papanas N AD - Diabetes Centre, Second Department of Internal Medicine, Democritus University of Thrace, Alexandroupolis, Greece. FAU - Papazoglou, Dimitrios AU - Papazoglou D AD - Diabetes Centre, Second Department of Internal Medicine, Democritus University of Thrace, Alexandroupolis, Greece. FAU - Roumeliotis, Athanasios AU - Roumeliotis A AD - Department of Nephrology, Democritus University of Thrace, Alexandroupolis, Greece. FAU - Panagoutsos, Stylianos AU - Panagoutsos S AD - Department of Nephrology, Democritus University of Thrace, Alexandroupolis, Greece. FAU - Thodis, Elias AU - Thodis E AD - Department of Nephrology, Democritus University of Thrace, Alexandroupolis, Greece. FAU - Theodoridis, Marios AU - Theodoridis M AD - Department of Nephrology, Democritus University of Thrace, Alexandroupolis, Greece. FAU - Pasadakis, Ploumis AU - Pasadakis P AD - Department of Nephrology, Democritus University of Thrace, Alexandroupolis, Greece. FAU - Maltezos, Eustratios AU - Maltezos E AD - Diabetes Centre, Second Department of Internal Medicine, Democritus University of Thrace, Alexandroupolis, Greece. FAU - Paschou, Peristera AU - Paschou P AD - Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis, Greece. FAU - Kotsa, Kalliopi AU - Kotsa K AD - Division of Endocrinology and Metabolism and Diabetes Center, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki, Greece. Electronic address: kalmanthou@yahoo.gr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20191123 PL - England TA - J Steroid Biochem Mol Biol JT - The Journal of steroid biochemistry and molecular biology JID - 9015483 RN - 0 (Receptors, Cell Surface) RN - 0 (intrinsic factor-cobalamin receptor) RN - 1406-16-2 (Vitamin D) SB - IM MH - Aged MH - Aged, 80 and over MH - Diabetes Mellitus, Type 2/blood/*genetics MH - Female MH - Genetic Predisposition to Disease MH - Greece MH - Humans MH - Male MH - Middle Aged MH - *Polymorphism, Single Nucleotide MH - Receptors, Cell Surface/*genetics MH - Vitamin D/*blood OTO - NOTNLM OT - Cubilin OT - Gene OT - SNP OT - Type 2 diabetes OT - Vitamin D COIS- Declaration of Competing Interest Authors report no conflict of interest. EDAT- 2019/11/27 06:00 MHDA- 2020/08/13 06:00 CRDT- 2019/11/27 06:00 PHST- 2019/08/10 00:00 [received] PHST- 2019/11/03 00:00 [revised] PHST- 2019/11/20 00:00 [accepted] PHST- 2019/11/27 06:00 [pubmed] PHST- 2020/08/13 06:00 [medline] PHST- 2019/11/27 06:00 [entrez] AID - S0960-0760(19)30468-6 [pii] AID - 10.1016/j.jsbmb.2019.105549 [doi] PST - ppublish SO - J Steroid Biochem Mol Biol. 2020 Apr;198:105549. doi: 10.1016/j.jsbmb.2019.105549. Epub 2019 Nov 23.