FBXW7 gene polymorphism is associated with type 2 diabetes in the Uygur population in Xinjiang, China

Abstract

Background FBXW7 gene expression is positively correlated with glycolipid metabolism and is associated with diabetes in animal models. In the current study, we focused on exploring whether genetic variants of the FBXW7 gene were associated with type 2 diabetes (T2DM) and the risk factors for T2DM in Uygur people in Xinjiang, China. Methods A total of 2164 Chinese Uygur subjects (673 T2DM patients and 1491 controls) were recruited for our case–control study, and four SNPs (rs10033601, rs2255137, rs2292743 and rs35311955) of the FBXW7 gene were genotyped using the improved multiplex ligation detection reaction (iMLDR) technique. Results Our study showed that the genotypes using the overdominant model (GA vs AA + GG) of rs10033601 and using the overdominant model (TA vs TT + AA) of rs2292743 were significantly different between T2DM patients and the controls (P = 0.005 and P = 0.012, respectively). After multivariate adjustments for confounders, the rs10033601 and rs2292743 SNPs were still independent risk factors for T2DM [GA vs AA + GG: odds ratio = 1.35, 95% confidence interval (CI) = 1.12–1.64, P = 0.002; TA vs TT + AA: OR = 1.28, 95% CI = 1.06–1.55, P = 0.011]. Participants within the Chinese Uygur populations and who with the GA genotype of rs10033601 and the TA genotype of rs2292743 were associated with significantly elevated glucose levels. Conclusions Our study revealed that both rs10033601 and rs2292743 of the FBXW7 gene were associated with T2DM in the Uygur populations in Xinjiang.

Smooth muscle NF90 deficiency ameliorates diabetic atherosclerotic calcification in male mice via FBXW7-AGER1-AGEs axis

“…5c ). Further, studies have reported that only FBXW7 among them is positively correlated with the homeostasis of glycolipid metabolism and pathogenesis of DM 29 – 31 . So, we identified the FBXW7 as a ubiquitin enzyme mediating NF90-induced ubiquitination degradation of AGER1.…”

“…In the current study, we revealed that AGEs increased the binding of NF90 with the 3’-UTR of FBXW7 mRNA and upregulated its expression. Some studies showed that FBXW7 is an E3 ubiquitin enzyme, and its expression is positively correlated with an imbalance in glycolipid metabolism, and is associated with diabetes 29 , 43 . However, other studies showed a beneficial role of FBXW7 in glucose homeostasis 30 , 44 .…”