Abstract
BackgroundRecent 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-β pathway in the arterial wall, a mechanism possibly causing vascular changes in diabetes.MethodsWe 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.ResultsAt 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.ConclusionOur data demonstrate that genetic polymorphism of the SLC2A10 gene is an independent risk factor for PAD in type 2 diabetes.
Highlights
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 transforming growth factor (TGF)-b pathway in the arterial wall, a mechanism possibly causing vascular changes in diabetes
Peripheral arterial disease (PAD) was defined as an ankle-brachial index (ABI) < 0.9 in any of the two limbs, using a handheld Doppler ultrasound (Medacord PVL, Medasonics, Fremont, CA) over brachial and dorsalis pedis or posterior tibial pulses according to the American College of Cardiology/American Heart Association guideline [13]
Combining all 11 markers, we identified a common haplotype (H4) conferring a strong risk of PAD in type 2 diabetic patients (P = 0.03, Odds ratios (OR): 14.5; 95% confidence intervals (CI): 1.3-160) (Table 3)
Summary
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-b pathway in the arterial wall, a mechanism possibly causing vascular changes in diabetes. Increased TGF-b signaling correlates with the microangiopathic changes and fibrosis seen in diabetic retinopathy, nephropathy, and peripheral arterial disease [9,10,11]. These data indicate that the SLC2A10 gene is a candidate gene of vascular complications in subjects with type 2 diabetes
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