Vitamin D pathway gene polymorphisms, vitamin D level, and cytokines in children with type 1 diabetes

Aims: The study aimed to examine genetic polymorphism of vitamin D-related genes and association between those genes and vitamin D and cytokines levels in children with type 1 diabetes (T1D). Materials and Methods: This study was conducted among 100 T1D children and 100 controls at Division of Endocrinology and Metabolism, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, during 2016 to 2018. Vitamin D metabolite levels were measured by liquid chromatography-tandem mass spectrometry method, serum cytokine levels of IFN-gamma, IL-10, IL-13, IL-17 alpha, IL-2, IL-4, IL-6, and TNF-alpha by immunoassay, and genetic variations at VDR, CYP2R1, CYP27B1, GC, DHCR7, and CYP24A1 by polymerase chain reaction-restriction fragment length polymorphism method. Results: A relationship between studied single nucleotide polymorphisms and T1D was found in CYP2R1 (rs10741657) (GA, OR: 1.83, 95% CI: 1.01-3.31; p = 0.04). VDR haplotypes were also remarkably different between T1D patients and controls. Controls had higher frequency of haplotype TACT than T1D patients (p = 0.02). Vitamin D and all cytokine levels, except for IL-17 alpha, were significantly increased in T1D compared to controls. The polymorphism of DHCR7 (rs12785878) was positively associated with 25OHD(3) and 3epi25OHD(3) levels and was negatively associated with 25OHD(2) level. On the other hand, polymorphism of CYP27B1 (rs4646536) was negatively associated with 3epi25OHD(3) level. Polymorphisms of CYP27B1 (rs4646536) and GC (rs2282679) were positively associated with TNF-alpha levels. VDR variation of rs1544410, rs731236, and rs7975232 also showed negative association with IL-10 levels. In contrast, the level of IL-10 was positively associated with DHCR7 (rs12785878). Conclusion: Relationships between T1D and CYP2R1 polymorphism and VDR haplotype were found. Vitamin D gene-related variations were associated with vitamin D and circulating cytokine levels in children with T1D.