A novel single nucleotide polymorphism in the protein tyrosine phosphatase N22 gene (PTPN22) is associated with Type 1 diabetes in a Chinese population

• Published in: Diabetic medicine Vol. 31; no. 2; pp. 219 - 226
• Main Authors: Pei, Z., Chen, X., Sun, C., Du, H., Wei, H., Song, W., Yang, Y., Zhang, M., Lu, W., Cheng, R., Luo, F.
• Format: Journal Article
• Language: English
• Published: Oxford Blackwell Publishing Ltd 01.02.2014; Blackwell; Wiley Subscription Services, Inc
• Subjects: Asian Continental Ancestry Group - genetics; Asian Continental Ancestry Group - statistics & numerical data; Biological and medical sciences; Case-Control Studies; Child; China - epidemiology; Diabetes; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - epidemiology; Diabetes Mellitus, Type 1 - genetics; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Genetic Association Studies; Genetic Heterogeneity; Genetic Predisposition to Disease; Glycated Hemoglobin A - metabolism; Humans; Linkage Disequilibrium; Male; Medical sciences; Polymorphism, Single Nucleotide; Protein Tyrosine Phosphatase, Non-Receptor Type 22 - genetics; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Asia; China; Endocrinopathy; Human; Immunopathology; Obesity; Nutrition; Enzyme; Nutrition disorder; Phosphoric monoester hydrolases; Autoimmune disease; Metabolic diseases; Esterases; Association; Type 1 diabetes; Hydrolases; Genetics; Single nucleotide polymorphism; Protein tyrosine phosphatase nonreceptor type 2; Endocrinology; Nutritional status; Protein-tyrosine-phosphatase; PTPN22 gene
• ISSN: 0742-3071; 1464-5491; 1464-5491
• DOI: 10.1111/dme.12331

Aims To examine single nucleotide polymorphisms in the protein tyrosine phosphatase N22 gene (PTPN22) and to study their association with Type 1 diabetes in a Chinese cohort. Methods Three hundred and sixty‐four young patients with Type 1 diabetes and 719 healthy children were included in this case‐controlled study. The genotypes of rs1217385, rs2488457 (–1123C>G), rs1217414, rs1217419, rs3765598 and rs2476601 (1858C>T) in the PTPN22 gene were determined using the SNaPshot method. Alleles, genotypes and haplotype frequencies were compared between patients with Type 1 diabetes and healthy control subjects. The association between single nucleotide polymorphisms and clinical traits/autoantibody status was also analysed. Results The single nucleotide polymorphism, rs1217419, located in the second intron of the PTPN22 gene was associated with Type 1 diabetes (odds ratio 1.5, 95% CI 1.14–1.97, P = 0.003). An additional single nucleotide polymorphism, rs1217385, was also associated with Type 1 diabetes; however, the association was secondary to that of rs1217419. The previously reported single nucleotide polymorphism that is associated with Type 1 diabetes (–1123G>C) had only marginal association with Type 1 diabetes in our study. A marginal association was also identified between –1123G>C and glutamic acid decarboxylase autoantibody positivity in patients with Type 1 diabetes. There was no association between the single nucleotide polymorphism 1858C>T and Type 1 diabetes in our studied cohort. Conclusions Our study confirmed that PTPN22 is a gene that contributes to Type 1 diabetes susceptibility. The primary association occurs with single nucleotide polymorphism rs1217419 and there is clear heterogeneity of the association between PTPTN22 polymorphisms and Type 1 diabetes in a Chinese population compared with other populations. What's new? Our cohort is the largest Chinese cohort studied to date in this research field. A novel Type 1 diabetes‐associated single nucleotide polymorphism in the protein tyrosine phosphatase N22 gene (PTPN22) was identified. Our analysis clearly showed ethnic differences in PTPN22–Type 1 diabetes association compared with other populations.