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Evaluation of the genetic association of the PTPN22 R620W polymorphism in familial and sporadic systemic lupus erythematosus.
Arthritis Rheum. 2006 Aug; 54(8):2533-40.AR

Abstract

OBJECTIVE

The R620W (1858C-->T) polymorphism in PTPN22 has been implicated in type 1 diabetes mellitus, rheumatoid arthritis, Graves' disease, Hashimoto thyroiditis, autoimmune thyroid disease, and systemic lupus erythematosus (SLE). The aim of this study was to evaluate this polymorphism in patients with familial SLE and in those with sporadic SLE.

METHODS

A total of 4,981 DNA samples were genotyped (from 1,680 SLE patients, 1,834 family members, and 1,467 controls). Both population-based case-control and family-based association designs were used for the analyses.

RESULTS

In the European American familial SLE cohort, the minor 1858T allele was more common in randomly selected patients compared with controls (chi2= 5.61, P = 0.018, odds ratio [OR] 1.46, 95% confidence interval [95% CI] 1.07-1.99). The heterozygous C/T genotype was also more common in these European American patients compared with controls (OR 1.63, 95% CI 1.15-2.30). Family-based association tests showed preferential transmission of the 1858T allele to affected offspring (chi2 = 5.87, P = 0.015). In contrast, the frequency of the 1858T minor allele was not significantly increased in the European American patients with sporadic SLE compared with controls, nor did these patients have preferential transmission of the 1858T allele. Indeed, the difference in the 1858T allele frequency between patients with familial SLE and those with sporadic SLE was measurable (allelic chi2= 4.22, P = 0.04, OR 1.51, 95% CI 1.02-2.24). Our data also showed that among patients with SLE, the 1858T allele was separately associated with type 1 diabetes mellitus and with autoimmune thyroid disease, confirming the findings of other investigators.

CONCLUSION

The 1858T allele of PTPN22 is associated with familial SLE but not with sporadic SLE in European Americans, thereby potentially explaining previous contradictory reports.

Authors+Show Affiliations

Oklahoma Medical Research Foundation, and Department of Veterans Affairs Medical Center, Oklahoma City, Oklahoma 73104, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

16868974

Citation

Kaufman, Kenneth M., et al. "Evaluation of the Genetic Association of the PTPN22 R620W Polymorphism in Familial and Sporadic Systemic Lupus Erythematosus." Arthritis and Rheumatism, vol. 54, no. 8, 2006, pp. 2533-40.
Kaufman KM, Kelly JA, Herring BJ, et al. Evaluation of the genetic association of the PTPN22 R620W polymorphism in familial and sporadic systemic lupus erythematosus. Arthritis Rheum. 2006;54(8):2533-40.
Kaufman, K. M., Kelly, J. A., Herring, B. J., Adler, A. J., Glenn, S. B., Namjou, B., Frank, S. G., Dawson, S. L., Bruner, G. R., James, J. A., & Harley, J. B. (2006). Evaluation of the genetic association of the PTPN22 R620W polymorphism in familial and sporadic systemic lupus erythematosus. Arthritis and Rheumatism, 54(8), 2533-40.
Kaufman KM, et al. Evaluation of the Genetic Association of the PTPN22 R620W Polymorphism in Familial and Sporadic Systemic Lupus Erythematosus. Arthritis Rheum. 2006;54(8):2533-40. PubMed PMID: 16868974.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evaluation of the genetic association of the PTPN22 R620W polymorphism in familial and sporadic systemic lupus erythematosus. AU - Kaufman,Kenneth M, AU - Kelly,Jennifer A, AU - Herring,Billy J, AU - Adler,Adam J, AU - Glenn,Stuart B, AU - Namjou,Bahram, AU - Frank,Summer G, AU - Dawson,Sarah L, AU - Bruner,Gail R, AU - James,Judith A, AU - Harley,John B, PY - 2006/7/27/pubmed PY - 2006/9/20/medline PY - 2006/7/27/entrez SP - 2533 EP - 40 JF - Arthritis and rheumatism JO - Arthritis Rheum. VL - 54 IS - 8 N2 - OBJECTIVE: The R620W (1858C-->T) polymorphism in PTPN22 has been implicated in type 1 diabetes mellitus, rheumatoid arthritis, Graves' disease, Hashimoto thyroiditis, autoimmune thyroid disease, and systemic lupus erythematosus (SLE). The aim of this study was to evaluate this polymorphism in patients with familial SLE and in those with sporadic SLE. METHODS: A total of 4,981 DNA samples were genotyped (from 1,680 SLE patients, 1,834 family members, and 1,467 controls). Both population-based case-control and family-based association designs were used for the analyses. RESULTS: In the European American familial SLE cohort, the minor 1858T allele was more common in randomly selected patients compared with controls (chi2= 5.61, P = 0.018, odds ratio [OR] 1.46, 95% confidence interval [95% CI] 1.07-1.99). The heterozygous C/T genotype was also more common in these European American patients compared with controls (OR 1.63, 95% CI 1.15-2.30). Family-based association tests showed preferential transmission of the 1858T allele to affected offspring (chi2 = 5.87, P = 0.015). In contrast, the frequency of the 1858T minor allele was not significantly increased in the European American patients with sporadic SLE compared with controls, nor did these patients have preferential transmission of the 1858T allele. Indeed, the difference in the 1858T allele frequency between patients with familial SLE and those with sporadic SLE was measurable (allelic chi2= 4.22, P = 0.04, OR 1.51, 95% CI 1.02-2.24). Our data also showed that among patients with SLE, the 1858T allele was separately associated with type 1 diabetes mellitus and with autoimmune thyroid disease, confirming the findings of other investigators. CONCLUSION: The 1858T allele of PTPN22 is associated with familial SLE but not with sporadic SLE in European Americans, thereby potentially explaining previous contradictory reports. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/16868974/Evaluation_of_the_genetic_association_of_the_PTPN22_R620W_polymorphism_in_familial_and_sporadic_systemic_lupus_erythematosus_ L2 - https://doi.org/10.1002/art.21963 DB - PRIME DP - Unbound Medicine ER -