Evaluation of the genetic association of the PTPN22 R620W polymorphism in familial and sporadic systemic lupus erythematosus

Abstract

Objective. The R620W (1858C3 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 casecontrol 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 ( 2 ‫؍‬ 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 ( 2 ‫؍‬ 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 2 ‫؍‬ 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.

Association analysis of the PTPN22 gene in childhood-onset systemic lupus erythematosus in Mexican population

“…However, the association of the T allele with childhood-onset SLE susceptibility was stronger (odds ratio (OR) 3.09, 95% confidence interval (95% CI) 1.32À7.21), than that reported in previous studies including mainly adultonset SLE (ORs ranging from 1.42 to 2.56). [7][8][9][10]18 Although the relative lower effect of this polymorphism on adultonset SLE compared with our pediatric SLE population may be explained by differences in the genetic background between the different ethnic populations, it also could be that some polymorphisms may have different effect in childhood-onset and adult-onset SLE. Actually, Wu et al 17 observed a younger age at diagnosis in one of their cohorts when stratified by CT/TT versus CC genotype.…”

“…10 In contrast, Wu et al 17 did not find association of the PTPN22 1858T polymorphism with sporadic SLE in Caucasian individuals from northern America, the UK and Finland, neither in familial SLE cases from northern America and Finland. However, Kaufman et al 18 recently reported that this polymorphism is associated with familial but not with sporadic SLE in European American patients. The previous studies included mainly adult-onset SLE patients, and to our knowledge there are no studies that include only pediatric-onset SLE patients.…”

Interferon regulatory factor-5 is genetically associated with systemic lupus erythematosus in African Americans

“…We included 4870 participants (1829 sporadic SLE cases and 3041 controls) enrolled with informed consent into the Lupus Genetics Studies at the OMRF as described previously 32 and the CASSLE case-control study collected at UAB (coordinating center), Northwestern University (Chicago, IL, USA), Johns Hopkins University (Baltimore, MD, USA), University of Texas-Houston Health Sciences Center and the University of Puerto Rico (San Juan, PR, USA) ( Table 6). OMRF also included 113 cases (51 Caucasians, 62 African Americans) and 82 controls (39 Caucasians, 13 African Americans) provided by the University of Texas Southwestern (UTSW) Medical Center.…”

Meta-analysis reveals an association of PTPN22 C1858T with autoimmune diseases, which depends on the localization of the affected tissue

“…Of the 14 case-control studies recruited for this study, 4,54,60,[103][104][105][106][107][108] 9 showed a significant association between PTPN22 C1858T and SLE. Meta-analysis showed a strong association between the T allele and SLE (OR ¼ 1.46; 95% CI ¼ 1.31-1.62, P ¼ 7.33 Â 10-13), although this was not as strong as that between T1D and PTPN22 C1858T or RA and PTPN22 C1858T (Figure 2c).…”