The systemic lupus erythematosus–associated <i>PDCD1</i> polymorphism PD1.3A in lupus nephritis

Prokunina, Ludmila; Gunnarsson, Iva; Sturfelt, Gunnar; Truedsson, Lennart; Seligman, Victoria A.; Olson, Jean L.; Seldin, Michael F.; Criswell, Lindsey A.; Alarcón‐Riquelme, Marta E.

doi:10.1002/art.11442

Cited by 77 publications

(66 citation statements)

References 8 publications

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“…We have thus demonstrated that PD-1.3A is a susceptibility factor for SLE (8), for lupus nephritis (9), and for a subgroup of RA patients negative for RF and the SE.…”

Section: Discussionmentioning

confidence: 56%

“…In patients with RA who were both RF negative and SE negative, the frequency of the A allele of PD-1.3 was 12.1%. This frequency was significantly different from that among controls (P ϭ 0.0054 [corrected P ϭ 0.015]) and the remaining groups of RA patients (P ϭ 0.023), and was similar to the frequency observed in patients with sporadic SLE (11.5%) (8,9). These results may indicate that different autoimmune diseases, such as SLE and RA, could share similar disease mechanisms.…”

mentioning

confidence: 50%

“…Allele A of SNP PD-1.3 disrupts binding of the Runx1 transcription factor to the enhancer and thereby alters the regulation of gene expression. This A allele was shown to be associated with systemic lupus erythematosus (SLE) and lupus nephritis, primarily in Europeans (8,9). Later, the same allele was also shown to be associated with diabetes (10).…”

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confidence: 99%

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Association of the PD‐1.3A allele of the PDCD1 gene in patients with rheumatoid arthritis negative for rheumatoid factor and the shared epitope

Prokunina¹,

Padyukov²,

Bennet³

et al. 2004

Arthritis & Rheumatism

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155

102

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Objective. To study the frequency of allele A of polymorphism PD-1.3 of the PDCD1 gene in patients with rheumatoid arthritis (RA) and its subsets, based on the presence of rheumatoid factor (RF) and the shared epitope (SE) alleles.Methods. A total of 1,175 patients with RA and 3,404 controls were genotyped for the PD-1.3 A/G polymorphism, which previously was identified as being involved in susceptibility to systemic lupus erythematosus (SLE) in patients of European descent.Results. We first detected a trend for association of allele A of the single-nucleotide polymorphism PD-1. Conclusion. Patients negative for both RF and the SE alleles showed association with the same allele that we previously identified as being involved in susceptibility to SLE. These results provide the first evidence of the involvement of the human PDCD1 gene in arthritis.

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“…We have thus demonstrated that PD-1.3A is a susceptibility factor for SLE (8), for lupus nephritis (9), and for a subgroup of RA patients negative for RF and the SE.…”

Section: Discussionmentioning

confidence: 56%

mentioning

confidence: 50%

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Association of the PD‐1.3A allele of the PDCD1 gene in patients with rheumatoid arthritis negative for rheumatoid factor and the shared epitope

Prokunina¹,

Padyukov²,

Bennet³

et al. 2004

Arthritis & Rheumatism

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155

102

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“…The PDCD1 PD1.3A allele has been associated with SLE susceptibility in Swedish, Mexican and European American cohorts, 6,7 whereas it has been shown to be protective for SLE among a Spanish cohort, 15 and not associated with SLE susceptibility among a biethnic (African American and Caucasian) US cohort. 9 The PD1.3A allele has also been positively associated with susceptibility to LN among Swedish Europeans 7,8 and negatively associated with APLA presence.…”

Section: Discussionmentioning

confidence: 96%

“…6 Further investigation of this gene variant has shown positive association in case-control analyses with lupus nephritis (LN) in two separate Swedish cohorts 7,8 but not in a US cohort of European American descent. 7 Furthermore, a bi-ethnic (African American and European American) case-control cohort revealed a protective association of the PD1.3A allele with presence of antiphospholipid antibodies (APLAs). 9 This same cohort failed to show an association between PD1.3A and SLE susceptibility.…”

Section: Introductionmentioning

confidence: 99%

Association of PDCD1 genetic variation with risk and clinical manifestations of systemic lupus erythematosus in a multiethnic cohort

et al. 2007

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We evaluated the roles of five single-nucleotide polymorphisms (SNPs) within PDCD1, and haplotypes defined by these SNPs, for the development of systemic lupus erythematosus (SLE) and specific sub-phenotypes (nephritis, antiphospholipid antibody positive, arthritis and double-stranded DNA positive) within a multiethnic US cohort of 1036 patients. Family based analyses were performed using 844 simplex families from four ethnic groups (Caucasian, Asian, Hispanic and African American). Subjects were genotyped for five 'tag' SNPs (selected from 15) to provide complete genetic information in all main ethnic groups. We employed transmission disequilibrium testing to assess risk for SLE by allele or haplotype, and multiple logistic regression analysis of SLE cases to examine associations with specific sub-phenotypes. In family based analyses, a haplotype containing the PD1.3A allele was significantly associated with SLE susceptibility among Caucasian families (P ¼ 0.01). Among Hispanic families, two novel SNPs were associated with SLE risk (P ¼ 0.005 and 0.01). In multivariate logistic regression analyses, five haplotypes were associated with specific sub-phenotypes among the different ethnic groups. These results suggest that PDCD1 genetic variation influences the risk and expression of SLE and that these associations vary according to ethnic background.

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A PD‐1 polymorphism is associated with disease progression in multiple sclerosis

Kroner

Mehling

Hemmer

et al. 2005

Annals of Neurology

213

152

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T cells are considered to play a pivotal role in orchestrating the self-reactive immune responses in multiple sclerosis (MS). Programmed death 1 (PD-1) is a member of the B7/CD28 superfamily of costimulatory molecules exerting inhibitory functions on T cells. Recently, an intronic 7146G/A polymorphism within the PD-1 gene was described and suggested to be associated with autoimmunity. We investigated whether this genetic polymorphism is a genetic modifier for risk and progression of MS. Blood samples from 939 German MS patients (mean age, 39 years; range, 13-71; 566 patients [60%] with relapsing-remitting MS, 279 (30%) with secondary, and 94 (10%) with primary progressive MS) and 272 healthy white controls were tested. Genotyping was performed by polymerase chain reaction and restriction enzyme digestion; results were confirmed by automatic sequencing. A significant association of the mutated allele with a progressive disease course was detected (44% 7146G vs 56% 7146A, chi(2) p = 0.002). Consequences of the PD-1 mutation for T-cell function were assessed ex vivo in some patients using microsphere-stimulated peripheral blood lymphocytes and purified CD4 cells. Importantly, PD-1-mediated inhibition of T-cell cytokine secretion (interferon-gamma) is impaired in patients carrying the PD-1 polymorphism. In conclusion, our data suggest that PD-1 polymorphism is a genetic modifier of the progression of MS, possibly through inducing a partial defect in PD-1-mediated inhibition of T-cell activation.

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The systemic lupus erythematosus–associated PDCD1 polymorphism PD1.3A in lupus nephritis

Cited by 77 publications

References 8 publications

Association of the PD‐1.3A allele of the PDCD1 gene in patients with rheumatoid arthritis negative for rheumatoid factor and the shared epitope

Association of the PD‐1.3A allele of the PDCD1 gene in patients with rheumatoid arthritis negative for rheumatoid factor and the shared epitope

Association of PDCD1 genetic variation with risk and clinical manifestations of systemic lupus erythematosus in a multiethnic cohort

A PD‐1 polymorphism is associated with disease progression in multiple sclerosis

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