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Zinc Transporter-8 Gene (SLC30A8) Is Associated with Type 2 Diabetes in Chinese

Shanghai Clinical Center for Endocrine and Metabolic Diseases (J.X., X.-Y.L., M.X., J.H., Y.H., J.-R.T., X.L., M.D., G.N.), Shanghai Institute of Endocrinology and Metabolism and Shanghai Key Laboratory for Endocrine Tumors, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China; and Department of Molecular and Clinical Genetics (B.Y.), Royal Prince Alfred Hospital and Central Clinical School, University of Sydney, Sydney 2050, Australia

Address all correspondence and requests for reprints to: Guang Ning, M.D., Ph.D., Department of Endocrinology and Metabolism, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Rui-Jin 2nd Road, Shanghai 200025, China. E-mail: guangning{at}medmail.com.cn.

Context: Several genome-wide association studies identified a strong association of SLC30A8 with type 2 diabetes in individuals of European ancestry. The effect of the association of rs13266634 with type 2 diabetes or related glycemic traits has not been fully extended to non-European populations, and a comprehensive examination of common variants in the gene has not yet been carried out in Han Chinese.

Objective: The objective of the study was to investigate the association of SLC30A8 with type 2 diabetes in Chinese.

Design: A comprehensive gene-based association study was performed using 14 tagging single-nucleotide polymorphism (SNPs) of SLC30A8 in Han Chinese subjects with normal glucose tolerance (NGT; n = 721), impaired glucose regulation (IGR; n = 375), and type 2 diabetes (n = 521).

Results: A significant association for SNP rs13266634 was observed between patients with type 2 diabetes and NGT controls (P = 0.016). The association was also observed between combined type 2 diabetes/IGR and NGT subjects (P = 0.002). The adjusted odds ratios for homozygote CC vs. TT at this locus were 1.71 for type 2 diabetes (95% confidence interval 1.19–2.45, P = 0.002) and 1.77 for type 2 diabetes and IGR (95% confidence interval 1.29–2.42, P = 0.0001). We further studied the genotype-phenotype correlation in 70 Han Chinese using iv glucose tolerance test and found an association between SNP rs13266634 and acute insulin response to glucose and disposition index (adjusted P = 0.012 and 0.004, respectively).

Conclusions: Our results provide evidence that SLC30A8 is a susceptible locus for type 2 diabetes in Chinese population, and its variant can influence insulin secretion.