Research Article 
A novel single nucleotide polymorphism in the protein tyrosine phosphatase N22 gene (PTPN22) is associated with Type 1 diabetes in a Chinese population
Z. Pei, X. Chen, C. Sun, H. Du, H. Wei, W. Song, Y. Yang, M. Zhang, W. Lu, R. Cheng and F. Luo
Diabetic Medicine, 2014, 31(2), 219-226. DOI: 10.1111/dme.12331
Abstract
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.
ASCI-ID: 109-1450
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Arterial stiffness and endothelial dysfunction independently and synergistically predict cardiovascular and renal outcome in patients with type 1 diabetesDiabetic Medicine, 2012, 29(8), 990-994. DOI: 10.1111/j.1464-5491.2012.03633.x
The effect of rising vs. falling glucose level on amperometric glucose sensor lag and accuracy in Type 1 diabetesDiabetic Medicine, 2012, 29(8), 1067-1073. DOI: 10.1111/j.1464-5491.2011.03545.x
Experiences of using blood glucose targets when following an intensive insulin regimen: a qualitative longitudinal investigation involving patients with Type 1 diabetesDiabetic Medicine, 2012, 29(8), 1079-1084. DOI: 10.1111/j.1464-5491.2012.03670.x
Temporal changes in the diagnosis of type 1 diabetes by diabetic ketoacidosis in Brazil: A nationwide surveyDiabetic Medicine, 2012, 29(9), 1142-1147. DOI: 10.1111/j.1464-5491.2012.03590.x
Does severe hypoglycaemia influence microvascular complications in Type 1 diabetes? An analysis of the Diabetes Control and Complications Trial databaseDiabetic Medicine, 2012, 29(9), 1195-1198. DOI: 10.1111/j.1464-5491.2012.03612.x
Number and sex ratio of children and impact of parental diabetes in individuals with Type 1 diabetesDiabetic Medicine, 2012, 29(10), 1268-1271. DOI: 10.1111/j.1464-5491.2012.03618.x
Type 1 diabetes in pre-school children - long-term metabolic control, associated autoimmunity and complicationsDiabetic Medicine, 2012, 29(10), 1291-1296. DOI: 10.1111/j.1464-5491.2012.03682.x
Facilitating children's contributions in clinic? Findings from an in-depth qualitative study with children with Type 1 diabetesDiabetic Medicine, 2012, 29(10), 1303-1310. DOI: 10.1111/j.1464-5491.2012.03714.x
Setting research priorities for Type 1 diabetesDiabetic Medicine, 2012, 29(10), 1321-1326. DOI: 10.1111/j.1464-5491.2012.03755.x
Femoral-gluteal adiposity is not associated with insulin sensitivity in Type 1 diabetesDiabetic Medicine, 2012, 29(11), 1407-1411. DOI: 10.1111/j.1464-5491.2012.03728.x
Prevalence of ketoacidosis at diagnosis of childhood onset Type 1 diabetes in Wales from 1991 to 2009 and effect of a publicity campaignDiabetic Medicine, 2012, 29(12), 1506-1509. DOI: 10.1111/j.1464-5491.2012.03638.x
The risk of proliferative retinopathy in siblings with Type 1 diabetesDiabetic Medicine, 2012, 29(12), 1567-1573. DOI: 10.1111/j.1464-5491.2012.03768.x
Type 1 diabetes from bench to bedside; a dedication to George EisenbarthDiabetic Medicine, 2013, 30(2), 133-133. DOI: 10.1111/dme.12101
The multiple origins of Type 1 diabetesDiabetic Medicine, 2013, 30(2), 135-146. DOI: 10.1111/dme.12081
Immunological pathways to β-cell damage in Type 1 diabetesDiabetic Medicine, 2013, 30(2), 147-154. DOI: 10.1111/dme.12085
The environment and the origins of islet autoimmunity and Type 1 diabetesDiabetic Medicine, 2013, 30(2), 155-160. DOI: 10.1111/dme.12099
Primary and secondary prevention of Type 1 diabetesDiabetic Medicine, 2013, 30(2), 161-169. DOI: 10.1111/dme.12100
Potential role of non-insulin adjunct therapy in Type 1 diabetesDiabetic Medicine, 2013, 30(2), 179-188. DOI: 10.1111/j.1464-5491.2012.03744.x
Eating problems in adolescents with Type 1 diabetes: a systematic review with meta-analysisDiabetic Medicine, 2013, 30(2), 189-198. DOI: 10.1111/j.1464-5491.2012.03771.x
Prevalence of depression among young people with Type 1 diabetes: a systematic reviewDiabetic Medicine, 2013, 30(2), 199-208. DOI: 10.1111/j.1464-5491.2012.03721.x
Self-treating hypoglycaemia: a longitudinal qualitative investigation of the experiences and views of people with Type 1 diabetesDiabetic Medicine, 2013, 30(2), 209-215. DOI: 10.1111/dme.12007
Insulin analogues in children with Type 1 diabetes: a 52-week randomized clinical trialDiabetic Medicine, 2013, 30(2), 216-225. DOI: 10.1111/dme.12041
The impact of blood glucose and HbA1c goals on glycaemic control in children and adolescents with Type 1 diabetesDiabetic Medicine, 2013, 30(3), 333-337. DOI: 10.1111/dme.12083
The effect of insulin intensification in children and young persons with Type 1 diabetes differs in relation to ethnic group; a prospective observational studyDiabetic Medicine, 2013, 30(4), 495-501. DOI: 10.1111/dme.12022
Urinary sulphate excretion and progression of diabetic nephropathy in Type 1 diabetesDiabetic Medicine, 2013, 30(5), 563-566. DOI: 10.1111/dme.12131
Characterizing the transition from paediatric to adult care among emerging adults with Type 1 diabetesDiabetic Medicine, 2013, 30(5), 610-615. DOI: 10.1111/dme.12067
Clinical and socio-demographic factors associated with diabetic ketoacidosis hospitalization in adults with Type 1 diabetesDiabetic Medicine, 2013, 30(5), 567-573. DOI: 10.1111/dme.12127
HLA class II gene associations in African American Type 1 diabetes reveal a protective HLA-DRB1*03 haplotypeDiabetic Medicine, 2013, 30(6), 710-716. DOI: 10.1111/dme.12148
Type 1 diabetes structured education: what are the core self-management behaviours?Diabetic Medicine, 2013, 30(6), 724-730. DOI: 10.1111/dme.12164
Blood β-hydroxybutyrate vs. urine acetoacetate testing for the prevention and management of ketoacidosis in Type 1 diabetes: a systematic reviewDiabetic Medicine, 2013, 30(7), 818-824. DOI: 10.1111/dme.12136
Vitamin D levels during and after resolution of ketoacidosis in children with new onset Type 1 diabetesDiabetic Medicine, 2013, 30(7), 829-834. DOI: 10.1111/dme.12200
Compromised quality of life in patients with both Type 1 diabetes mellitus and coeliac diseaseDiabetic Medicine, 2013, 30(7), 835-839. DOI: 10.1111/dme.12205
Serological testing for coeliac disease in Type 1 diabetes mellitus: is immunoglobulin A level measurement necessary?Diabetic Medicine, 2013, 30(7), 840-845. DOI: 10.1111/dme.12163
Blood pressure levels but not hypertensive complications have increased in Type 1 diabetes pregnancies during 1989-2010Diabetic Medicine, 2013, 30(9), 1087-1093. DOI: 10.1111/dme.12224
Hypoglycaemia, fear of hypoglycaemia and quality of life in children with Type 1 diabetes and their parentsDiabetic Medicine, 2013, 30(9), 1126-1131. DOI: 10.1111/dme.12247
Diabetes distress in Type 1 diabetes-a new measurement fit for purposeDiabetic Medicine, 2013, 30(9), 1132-1139. DOI: 10.1111/dme.12241
Disclosure of psychosocial stressors affecting diabetes care among uninsured young adults with Type 1 diabetesDiabetic Medicine, 2013, 30(9), 1140-1144. DOI: 10.1111/dme.12248
Vitamin D in youth with Type 1 diabetes: prevalence of insufficiency and association with insulin resistance in the SEARCH Nutrition Ancillary StudyDiabetic Medicine, 2013, 30(11), 1324-1332. DOI: 10.1111/dme.12297
Concordance of retinopathy and nephropathy over time in Type 1 diabetes: an analysis of data from the Diabetes Control and Complications TrialDiabetic Medicine, 2013, 30(11), 1333-1341. DOI: 10.1111/dme.12296
Factors associated with diabetic ketoacidosis at onset of Type 1 diabetes in children and adolescentsDiabetic Medicine, 2013, 30(11), 1360-1366. DOI: 10.1111/dme.12252
Real-time continuous glucose monitoring during labour and delivery in women with Type 1 diabetes - observations from a randomized controlled trialDiabetic Medicine, 2013, 30(11), 1374-1381. DOI: 10.1111/dme.12246
Paediatric estimated average glucose in children with Type 1 diabetesDiabetic Medicine, 2014, 31(1), 36-39. DOI: 10.1111/dme.12285
Impact of continuous glucose monitoring on diabetes management and marital relationships of adults with Type 1 diabetes and their spouses: a qualitative studyDiabetic Medicine, 2014, 31(1), 47-54. DOI: 10.1111/dme.12276
Diabetes-Oriented Learning Family Intervention (DOLFIN): a feasibility study evaluating an intervention for carers of young persons with Type 1 diabetesDiabetic Medicine, 2014, 31(1), 55-60. DOI: 10.1111/dme.12333
Developing a hierarchy of needs for Type 1 diabetesDiabetic Medicine, 2014, 31(1), 61-67. DOI: 10.1111/dme.12284
Patients with Type 1 diabetes consuming alcoholic spirits have an increased risk of microvascular complicationsDiabetic Medicine, 2014, 31(2), 156-164. DOI: 10.1111/dme.12307
The dynamic changes of zinc transporter 8 autoantibodies in Czech children from the onset of Type 1 diabetes mellitusDiabetic Medicine, 2014, 31(2), 165-171. DOI: 10.1111/dme.12308
Medical and psychological outcomes for young adults with Type 1 diabetes: no improvement despite recent advances in diabetes careDiabetic Medicine, 2014, 31(2), 227-231. DOI: 10.1111/dme.12305
Urinary type IV collagen as a predictor for the incidence of microalbuminuria in young patients with Type 1 diabetesDiabetic Medicine, 2014, 31(2), 213-218. DOI: 10.1111/dme.12317
Real-time continuous glucose monitoring as a tool to prevent severe hypoglycaemia in selected pregnant women with Type 1 diabetes - an observational studyDiabetic Medicine, 2014, 31(3), 352-356. DOI: 10.1111/dme.12383
Epidemiology of childhood Type 1 diabetes in Taiwan, 2003 to 2008Diabetic Medicine, 2014, 31(6), 666-673. DOI: 10.1111/dme.12407
Plateau of adiposity in Australian children diagnosed with Type 1 diabetes: a 20-year studyDiabetic Medicine, 2014, 31(6), 686-690. DOI: 10.1111/dme.12402
Use of clinical targets in diabetes patient education: qualitative analysis of the expectations and impact of a structured self-management programme in Type 1 diabetesDiabetic Medicine, 2014, 31(6), 733-738. DOI: 10.1111/dme.12401
Substantial reductions in the number of diabetic ketoacidosis and severe hypoglycaemia episodes requiring emergency treatment lead to reduced costs after structured education in adults with Type 1 diabetesDiabetic Medicine, 2014, 31(7), 847-853. DOI: 10.1111/dme.12441
Effects of advanced carbohydrate counting in patients with Type 1 diabetes: a systematic reviewDiabetic Medicine, 2014, 31(8), 886-896. DOI: 10.1111/dme.12446
Reductions in resistance exercise-induced hyperglycaemic episodes are associated with circulating interleukin-6 in Type 1 diabetesDiabetic Medicine, 2014, 31(8), 1009-1013. DOI: 10.1111/dme.12462