ABSTRACT. We investigated the association between macrophage migration inhibitory factor (MIF) rs1007888 single-nucleotide polymorphisms and the genetic susceptibility to gestational diabetes mellitus (GDM). A total of 240 GDM pregnant women (GDM group) and 330 healthy pregnant women (control group) were included in the study. Differences in the MIF rs1007888 genotype and allele frequencies and differences between fasting blood glucose, fasting insulin, homeostatic model assessment (HOMA)-insulin resistance, and HOMA-b levels of pregnant women with different genotypes were compared. MIF genotype distributions were significantly different in the GDM group compared to the control group (P < 0.05). No significant difference was observed in the allele distributions of MIF rs1007888 between the GDM group and control group (P > 0.05). GDM patients had higher fasting blood glucose, fasting insulin, and HOMA-insulin resistance levels, but lower HOMA-b levels than normal gestational women (P < 0.05). Fasting blood glucose, fasting insulin, and HOMA-insulin resistance in pregnant women with the GG genotype were significantly higher than those with GA and AA genotypes, while HOMA-b in pregnant women with the GG genotype was lower (all P < 0.05). Our findings demonstrated the associations among MIF polymorphism rs1007888, insulin resistance, and pancreatic β cell functions in GDM patients. The GG genotype of MIF rs1007888 may be a genetic susceptibility factor in the pathogenesis of GDM.

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statement: We generated a carotid collar placement atherosclerosis model in the novel spontaneous HU Uox-KO mouse and demonstrate that urate plays a contributing rather than a causal role in the carotid neointimal lesions, while urate-lowering treatment may bring additional benefits in this HU mouse model. Abstract Hyperuricemia (HU) is a cause of gout. Clinical studies show a link between HU and cardiovascular disease. However, the role of soluble serum urate on atherosclerosis development remains elusive. We aimed to use a new HU mouse model (Uricase/Uox knockout (KO)) to further investigate the relationship between HU and atherosclerosis.Mouse model of induced carotid atherosclerosis was established in the novel spontaneous HU Uox-KO mouse and their wild type littermates (C57BL/6J background). Mice were implanted with a perivascular collar placement around the right carotid artery in combination with a western-type diet. To investigate urate-lowering treatment (ULT) effects on intima, the mice were gavaged daily from the age of 6 weeks with allopurinol. Human umbilical vein endothelial cells (HUVECs) were co-incubated with soluble urate, with and without probenecid, to study the mechanism of urate-related atherosclerosis. The Uox-KO mice had significantly elevated serum urate levels combined with higher blood urea nitrogen and serum creatinine. Western blot analysis showed enhanced levels of atherosclerosis inflammatory response proteins. However, there were no other risk indicators for the pathogenesis of atherosclerosis, including increased fasting glucose, altered lipid and atherosclerosis characterized cardiovascular and histological manifestations. In contrast, collar placement Uox-KO mice showed severe neointimal changes in histology staining consistent with increases in intimal area and increases in proliferating cell nuclear antigen (PCNA) -and F4/80-positive cells. Allopurinol reduced neointimal areas induced by the perivascular collar in hyperuricemic mice accompanied by decreased expression of PCNAand F4/80-positive cells (P< 0.05). ULT alleviated atherosclerosis inflammatory response factors and reactive oxygen species intensities in both collar placement Uox-KO mice and urate-stimulated HUVECs. In vitro results using HUVECs showed ROS was induced by urate and ROS induction was abrogated using antioxidants. These data demonstrate that urate per se does not trigger atherosclerosis intima lesions in mice. Urate worsens carotid neointimal lesions induced by the perivascular collar and urate-lowering therapy partially abrogates the effects. The current study warrants the further human based study on the possible benefits of urate-lowering therapy in atherosclerosis patients with HU.