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-β 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.


CONCLUSIONS
Our data demonstrate that genetic polymorphism of the SLC2A10 gene is an independent risk factor for PAD in type 2 diabetes.
Jiang
Yi-Der
YD
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Chang
Yi-Cheng
YC
Chiu
Yen-Feng
YF
Chang
Tien-Jyun
TJ
Li
Hung-Yuan
HY
Lin
Wen-Hsing
WH
Yuan
Hsiang-Yu
HY
Chen
Yuan-Tsong
YT
Chuang
Lee-Ming
LM
D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000235:genetics*; D003925:Diabetic Angiopathies / Q000235:genetics*; D005260:Female; D005838:Genotype; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016491:Peripheral Vascular Diseases / Q000150:complications / Q000209:etiology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D012307:Risk Factors; D016212:Transforming Growth Factor beta / Q000235:genetics
D051246:Glucose Transport Proteins, Facilitative; C430746:SLC2A10 protein, human; D016212:Transforming Growth Factor beta