5-Lipoxygenase (ALOX5): Genetic susceptibility to type 2 diabetes and vitamin D effects on monocytes

• Published in: The Journal of steroid biochemistry and molecular biology 2019-03, Vol.187, p.52-57
• Main Authors: Nejatian, Nojan, Häfner, Ann-Kathrin, Shoghi, Firouzeh, Badenhoop, Klaus, Penna-Martinez, Marissa
• Format: Article
• Language: English
• Subjects: 1α,25-Dihydroxy vitamin D3; 25-Hydroxyvitamin D; Alleles; Arachidonate 5-lipoxygenase; C-reactive protein; Calcitriol; CD14 antigen; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Gene polymorphism; Hydrolase; IL-1β; Inflammatory diseases; Leukotriene A4 hydrolase; Leukotriene B4 receptor type 1; Leukotriene B4 receptors; Lipoxygenase; Metabolites; Monocytes; mRNA; Patients; Plasma levels; Polymorphism; Regulatory sequences; Therapeutic targets; Type 2 diabetes mellitus; Vitamin D
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/j.jsbmb.2018.10.022

•ALOX5 rs4987105 polymorphism is associated with T2D.•ALOX5 CC risk genotype is linked to lower vitamin D and increased CRP levels.•IL-1β + calcitriol treatment increased ALOX5, LTA4H and LTB4R1 mRNA expression.•ALOX5 andLTA4H mRNA expression were increased in T2D patients compared to HC. The arachidonate 5-lipoxygenase (ALOX5) pathway has been implicated in chronic inflammatory disease which may be influenced by vitamin D due to vitamin D response elements (VDRE). We investigated an ALOX5 polymorphism (rs4987105) in patients with type 2 diabetes (T2D) and the in vitro effects of calcitriol (1,25(OH)2D3) on ALOX5 metabolism in monocytes of T2D patients and healthy controls (HC). 533 T2D and 473 HC were genotyped for the rs4987105 polymorphism. In addition, the 25(OH)D3 and 1,25(OH)2D3 plasma levels were measured in both cohorts. Further C-reactive protein (CRP) was determined in T2D patients. Our results demonstrate, that genotype CC and the allele C of ALOX5 rs4987105 polymorphism were more frequent in T2D compared to HC (OR = 1.44; 95% CI: 1.12–1.84; p