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Am J Physiol Endocrinol Metab 294: E987-E992, 2008. First published March 18, 2008; doi:10.1152/ajpendo.90234.2008
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Polymorphisms in metallothionein-1 and -2 genes associated with the risk of type 2 diabetes mellitus and its complications

Lina Yang,1,* Hongyan Li,1,* Ting Yu,1 Haijun Zhao,1 M. George Cherian,1,2 Lu Cai,1,3 and Ya Liu1

1School of Public Health, Jilin University, Changchun, China; 2Department of Pathology, University of Western Ontario, London, Canada; and 3Departments of Medicine and Radiation Oncology, the University of Louisville, Louisville, Kentucky

Submitted 13 February 2008 ; accepted in final form 14 March 2008

Metallothionein (MT) as a potent antioxidant can affect energy metabolism. The present study was undertaken to investigate the association between MT gene polymorphism and type 2 diabetes mellitus. Using the PCR-based restriction fragment length polymorphism method, seven single nucleotide polymorphisms (SNPs) in MT genes (rs8052394 and rs11076161 in MT1A gene, rs8052334, rs964372, and rs7191779 in MT1B gene, rs708274 in MT1E gene, and rs10636 in MT2A gene) were detected in 851 Chinese people of Han descent (397 diabetes and 454 controls). Several serum measurements were also examined randomly for 43 diabetic patients and 41 controls. The frequency distributions of the G allele in SNP rs8052394 of MT1A gene were significantly associated with the incidence of type 2 diabetes. There was no difference between patients and controls for the rest of six SNPs. Serum levels of interleukin-6 and tumor necrosis factor-{alpha} were higher, and serum superoxide dismutase activity was significantly lower in the diabetic group than those in the control group. For diabetic patients, serum superoxide dismutase activity was significantly lower in GG or GA carriers than those of AA carriers of rs8052394 SNP. Increased serum levels in diabetic patients were positively associated with rs964372 SNP, and type 2 diabetes with neuropathy was positively associated with rs10636 and rs11076161. These results suggest that multiple SNPs in MT genes are associated with diabetes and its clinical symptoms. Furthermore, MT1A gene in rs8052394 SNP is most likely the predisposition gene locus for diabetes or changes of serum superoxide dismutase activity.

single nucleotide polymorphism; superoxide dismutase; diabetic complications


Address for reprint requests and other correspondence: Y. Liu, Dept. of Nutrition and Toxicology, The School of Public Health at Jilin University, 1163 Ximin St., Changchun 130021, China (e-mail: liuy{at}jlu.edu.cn); and L. Cai: 511 South Floyd St., MDR 533, Louisville, KY 40202 (e-mail: L0cai001{at}louisville.edu)






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