Association of programmed cell death 1 polymorphisms and systemic lupus erythematosus: a meta-analysis

Programmed cell death 1 (PDCD1 or PD1) polymorphisms have been inconsistently reported to be associated with systemic lupus erythematosus (SLE). The aim of this study was to explore whether the PDCD1 polymorphisms confer a susceptibility to SLE and lupus nephritis (LN). We conducted a meta-analysis on the association of PDCD1 polymorphisms with SLE in overall and specific ethnic populations. A total of 15 separate comparisons were included in this meta-analysis consisting of nine Europeans, two Latin Americans, two Africans, one Asian and one unknown participant. In subgroup analysis, the PD1.3A allele was significantly associated with SLE in Latin Americans (OR = 3.073, 95% CI = 1.416–6.461, P = 0.003), but not in patients of European and African decent. The PD1.3A allele was a risk factor for LN in European descendants (OR = 2.207, 95% CI = 1.488–3.467, P < 0.001). The PD1.5C allele was a risk factor for SLE in Europeans (OR = 1.297, 95% CI = 1.024–1.643, P = 0.031). In conclusion, this meta-analysis demonstrated an association of the PD1.3A allele with LN in European and SLE in Latin-American populations. Furthermore, the PD1.5C allele was associated with SLE susceptibility in Europeans.

[1]  J. Harley,et al.  Unraveling the genetics of systemic lupus erythematosus , 2006, Springer Seminars in Immunopathology.

[2]  J. Terwilliger,et al.  A susceptibility locus for human systemic lupus erythematosus (hSLE1) on chromosome 2q. , 2000, Journal of autoimmunity.

[3]  George Davey Smith,et al.  Meta-analysis: Principles and procedures , 1997, BMJ.

[4]  Marta E Alarcón-Riquelme,et al.  The systemic lupus erythematosus-associated PDCD1 polymorphism PD1.3A in lupus nephritis. , 2004, Arthritis and rheumatism.

[5]  G. Davey Smith,et al.  Meta-analyses of randomised controlled trials. , 1997, Lancet.

[6]  T. Honjo,et al.  Immunological studies on PD-1 deficient mice: implication of PD-1 as a negative regulator for B cell responses. , 1998, International immunology.

[7]  S. Thompson,et al.  Quantifying heterogeneity in a meta‐analysis , 2002, Statistics in medicine.

[8]  N. Laird,et al.  Meta-analysis in clinical trials. , 1986, Controlled clinical trials.

[9]  D. Sanghera,et al.  Role of an intronic polymorphism in the PDCD1 gene with the risk of sporadic systemic lupus erythematosus and the occurrence of antiphospholipid antibodies , 2004, Human Genetics.

[10]  S Duval,et al.  Trim and Fill: A Simple Funnel‐Plot–Based Method of Testing and Adjusting for Publication Bias in Meta‐Analysis , 2000, Biometrics.

[11]  Shih-Chang Lin,et al.  Association of a programmed death 1 gene polymorphism with the development of rheumatoid arthritis, but not systemic lupus erythematosus. , 2004, Arthritis and rheumatism.

[12]  T. Okazaki,et al.  PD-1/PD-L pathway and autoimmunity , 2005, Autoimmunity.

[13]  T. Honjo,et al.  Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. , 1999, Immunity.

[14]  Shu-Chen Wang,et al.  Programmed Death-1 Gene Polymorphisms in Patients With Systemic Lupus Erythematosus in Taiwan , 2006, Journal of Clinical Immunology.

[15]  G. Tsokos,et al.  Autoimmunity in systemic lupus erythematosus: integrating genes and biology. , 2006, Seminars in immunology.

[16]  Jesús K. Estrada-Gil,et al.  Association of PDCD1 polymorphisms with childhood-onset systemic lupus erythematosus , 2007, European Journal of Human Genetics.

[17]  L. Prokunina-Olsson,et al.  Association of PDCD1 genetic variation with risk and clinical manifestations of systemic lupus erythematosus in a multiethnic cohort , 2007, Genes and Immunity.

[18]  S. Rantapää-Dahlqvist,et al.  Association of a PDCD1 polymorphism with renal manifestations in systemic lupus erythematosus. , 2005, Arthritis and rheumatism.

[19]  C. Bonferroni.  Il calcolo delle assicurazioni su gruppi di teste , 1935 .

[20]  George Davey Smith,et al.  Meta-analysis of randomised controlled trials , 1997, The Lancet.

[21]  J. Gómez-Reino,et al.  Bias in association studies of systemic lupus erythematosus susceptibility due to geographical variation in the frequency of a programmed cell death 1 polymorphism across Europe , 2007, Genes and Immunity.

[22]  R. Jonsson,et al.  A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans , 2002, Nature Genetics.

[23]  Á. Carracedo,et al.  Association of PDCD1 with susceptibility to systemic lupus erythematosus: evidence of population-specific effects. , 2004, Arthritis and rheumatism.

[24]  A. Voss,et al.  A putative regulatory polymorphism in PD-1 is associated with nephropathy in a population-based cohort of systemic lupus erythematosus patients , 2004, Lupus.