SLC2A10 genetic polymorphism predicts development of peripheral arterial disease in patients with type 2 diabetes. SLC2A10 and PAD in type 2 diabetes

Background: Recent data indicate that loss-of-function mutation in the gene encoding the facilitative glucose transporter GLUT10 (SLC2A10) causes arterial tortuosity syndrome via upregulation of the TGF-beta pathway in the arterial wall, a mechanism possibly causing vascular changes in diabetes. Methods: We genotyped 10 single nucleotide polymorphisms and one microsatellite spanning 34 kb across the SLC2A10 gene in a prospective cohort of 372 diabetic patients. Their association with the development of peripheral arterial disease (PAD) in type 2 diabetic patients was analyzed. Results: At baseline, several common SNPs of SLC2A10 gene were associated with PAD in type 2 diabetic patients. A common haplotype was associated with higher risk of PAD in type 2 diabetic patients (haplotype frequency: 6.3%, P = 0.03; odds ratio [OR]: 14.5; 95% confidence interval [CI]: 1.3-160.7) at baseline. Over an average follow-up period of 5.7 years, carriers with the risk-conferring haplotype were more likely to develop PAD (P = 0.007; hazard ratio: 6.78; 95% CI: 1.66-27.6) than were non-carriers. These associations remained significant after adjustment for other risk factors of PAD. Conclusion: Our data demonstrate that genetic polymorphism of the SLC2A10 gene is an independent risk factor for PAD in type 2 diabetes.