<i>PTPN22</i> R620W Functional Variant in Type 1 Diabetes and Autoimmunity Related Traits

Chelala, Claude; Duchatelet, Sabine; Joffret, Marie-Line; Bergholdt, Regine; Dubois‐Laforgue, Danièle; Ghandil, Pegah; Pociot, Flemming; Caillat‐Zucman, Sophie; Timsit, José; Julier, Cécile

doi:10.2337/db06-0942

Cited by 62 publications

(46 citation statements)

References 29 publications

(34 reference statements)

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“…Note that in contrast with some other populations, the distribution of alleles ϩ1858CϾT and rs2488457 is informative in Sardinia, most likely owing to their distinct distribution on positively and neutrally associated haplotypes, respectively. Similar conclusions about the role of rs2488457 were recently reached by Chelala et al (32) after analyzing a pooled French, Danish, and U.S. sample set. Although Carlton et al (23) suggested an association of rheumatoid arthritis with polymorphisms rs1310182, rs3811021, and rs3789604, with the latter two alleles in nearly complete linkage disequilibrium with each other, when we genotyped two of these variants, rs1310182 (marker 11) and rs3811021 (marker 15), in the Sardinian families, we found no evidence of association with type 1 diabetes.…”

Section: ϫ02supporting

confidence: 83%

Further Evidence of a Primary, Causal Association of the PTPN22 620W Variant With Type 1 Diabetes

et al. 2008

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OBJECTIVE— The minor allele of the nonsynonymous single nucleotide polymorphism (SNP) +1858C>T within the PTPN22 gene is positively associated with type 1 diabetes and other autoimmune diseases. Genetic and functional data underline its causal effect, but some studies suggest that this polymorphism does not entirely explain disease association of the PTPN22 region. The aim of this study was to evaluate type 1 diabetes association within this gene in the Sardinian population. RESEARCH DESIGN AND METHODS— We resequenced the exons and potentially relevant portions of PTPN22 and detected 24 polymorphisms (23 SNPs and 1 deletion insertion polymorphism [DIP]), 8 of which were novel. A representative set of 14 SNPs and the DIP were sequentially genotyped and assessed for disease association in 794 families, 490 sporadic patients, and 721 matched control subjects. RESULTS— The +1858C>T variant, albeit rare in the general Sardinian population (allele frequency 0.014), was positively associated with type 1 diabetes (Pone tail = 3.7 × 10−3). In contrast, the background haplotype in which this mutation occurred was common (haplotype frequency 0.117) and neutrally associated with disease. We did not confirm disease associations reported in other populations for non +1858C>T variants (rs2488457, rs1310182, and rs3811021), although they were present in appreciable frequencies in Sardinia. Additional weak disease associations with rare variants were detected in the Sardinian families but not confirmed in independent case-control sample sets and are most likely spurious. CONCLUSIONS— We provide further evidence that the +1858C>T polymorphism is primarily associated with type 1 diabetes and exclude major contributions from other purportedly relevant variants within this gene.

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Section: ϫ02supporting

confidence: 83%

Further Evidence of a Primary, Causal Association of the PTPN22 620W Variant With Type 1 Diabetes

et al. 2008

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“…Previously, association between GADA and HLA-DQ2/HLA-DQ8 or HLA-DQ8 has been observed in healthy children (21,22,23) and adult-onset type 1 diabetic patients (21, 24) but not in children or adolescents with type 1 diabetes, in whom GADA is associated with DQ2 (14,24,25,26). Association between PTPN22 and GADA is reported in patients with long disease duration (27) but not in type 1 diabetic children (15,28). Of note, the frequencies of HLA and PTPN22 risk genotypes in the GADA-positive nondiabetic subjects were practically identical to the frequencies in GADA-positive LADA patients (29).…”

Section: Discussionmentioning

confidence: 99%

Association of variants in HLA-DQA1-DQB1, PTPN22, INS, and CTLA4 with GAD autoantibodies and insulin secretion in nondiabetic adults of the Botnia Prospective Study

Andersen

Lundgren

Isomaa

et al. 2012

European Journal of Endocrinology

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Objective: Previously, we observed an association between family history of type 1 diabetes and development of non-insulin-dependent diabetes. The aims of this study were to assess whether type 1 diabetes susceptibility gene variants explain this association and investigate the effect of the variants on insulin secretion and presence of glutamic acid decarboxylase autoantibodies (GADA) in nondiabetic adults. Design and methods: Polymorphisms in INS (rs689), PTPN22 (rs2476601), CTLA4 (rs3087243), and the HLA-DQA1-DQB1 regions (rs2187668 and rs7454108 tagging HLA-DQ2.5 and HLA-DQ8 respectively) were genotyped in the Botnia Prospective Study (nZ2764), in which initially nondiabetic participants were followed for a mean of 8.1 years. Results: The variants did not explain the association between family history of type 1 diabetes and development of non-insulin-dependent diabetes. In these nondiabetic adults, HLA-DQ and PTPN22 risk genotypes were associated with GADA (HLA-DQ2.5/HLA-DQ8 or HLA-DQ8: OR (95% CI): 1.7 (1.3-2.3), PZ0.0004; PTPN22 CT/TT: OR: 1.6 (1.2-2.2), PZ0.003; P values were adjusted for sex, age, BMI, and follow-up time). A higher genetic risk score was associated with lower insulin secretion (insulinogenic index: 13.27 (16.27) vs 12.69 (15.27) vs 10.98 (13.06), PZ0.02) and better insulin sensitivity index (risk score of 0-1 vs 2-3 vs 4-6: 142 (111) vs 144 (118) vs 157 (127), PZ0.01) at baseline and a poorer capacity to compensate for the increased insulin demand after follow-up. Conclusions: In nondiabetic adults, HLA-DQ2.5/HLA-DQ8 and PTPN22 CT/TT genotypes were associated with GADA.

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“…Several studies have found a significant association between a functional missense PTPN22 C1858T (R620W) polymorphism and vulnerability to numerous autoimmune diseases such as type 1 diabetes, rheumatoid arthritis and systemic lupus erythematosus (Gomez et al, 2005a;Chelala et al, 2007;Lee et al, 2007;Douroudis et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

R620W functional polymorphism of protein tyrosine phosphatase non-receptor type 22 is not associated with pulmonary tuberculosis in Zahedan, southeast Iran

Kouhpayeh

Hashemi²,

Hashemi³

et al. 2012

Genet. Mol. Res.

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ABSTRACT. The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene, which encodes an intracellular lymphoid-specific phosphatase, is considered an important regulator of T-cell activation. We investigated a possible association between the PTPN22 C1858T (R620W) polymorphism and pulmonary tuberculosis in an Iranian population. Single nucleotide polymorphisms of PTPN22 C1858T (rs2476601) were genotyped in 172 pulmonary tuberculosis cases and 204 normal subjects from Zaheden, Iran. Frequencies of genotypes CC, CT and TT of the PTPN22 C1858T polymorphism were 98.3, 1.7 and 0% in the pulmonary tuberculosis patients, and 96.1, 3.9 and 0% in the control group, respectively (P = 0.239). The frequency of the minor (T) allele was 0.8% in pulmonary tuberculosis patients and 2.0% in controls. Significant differences were not observed in genotype or allele frequencies of PTPN22 C1858T in the comparison between pulmonary tuberculosis patients and healthy subjects in our Iranian population sample.

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PTPN22 R620W Functional Variant in Type 1 Diabetes and Autoimmunity Related Traits

Cited by 62 publications

References 29 publications

Further Evidence of a Primary, Causal Association of the PTPN22 620W Variant With Type 1 Diabetes

Further Evidence of a Primary, Causal Association of the PTPN22 620W Variant With Type 1 Diabetes

Association of variants in HLA-DQA1-DQB1, PTPN22, INS, and CTLA4 with GAD autoantibodies and insulin secretion in nondiabetic adults of the Botnia Prospective Study

R620W functional polymorphism of protein tyrosine phosphatase non-receptor type 22 is not associated with pulmonary tuberculosis in Zahedan, southeast Iran

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