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

Genes & Immunity volume 8, pages 279–287 (2007)Cite this article

Abstract

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=0.01). Among Hispanic families, two novel SNPs were associated with SLE risk (P=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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Acknowledgements

Mexican Amerindians from the Mazateco area in the State of Guerrero, South Eastern Mexico were kindly provided by Dr Julio Granados Arriola (Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición ‘Salvador Zubirán’, México City, INCMNSZ). This work was supported by NIH R01 AR44804, K24 AR02175, ES09911, T32 DK07219, the Arthritis Foundation and the Mary Kirkland Center for Lupus Research. This work was also supported by grants from the Alliance for Lupus Research (to MEAR), The Swedish Research Council, the Swedish Association Against Rheumatism, the Magnus Bergwalls Foundation, The Gustaf V:e 80-Year Jubilee Foundation, the Marcus Borgströms Foundation and the Torsten and Ragnar Söderbergs Foundation. MEAR is a Research Fellow from the Royal Swedish Academy of Sciences supported by a grant from the Knut and Alice Wallenberg Foundation, Sweden. These studies were performed in part in the General Clinical Research Center, Moffitt Hospital, University of California, San Francisco, with funds provided by the National Center for Research Resources, 5 M01 RR-00079, US Public Health Service.

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Authors and Affiliations

  1. Department of Medicine, Rosalind Russell Medical Research Center for Arthritis, University of California, San Francisco, CA, USA

    C M Thorburn, K A Sterba, R F Lum & L A Criswell

  2. Genome Technology Branch, National Human Genome Research Institute, NIH, Bethesda, MD, USA

    L Prokunina-Olsson

  3. Department of Biochemistry and Molecular Medicine, Rowe Program in Human Genetics, University of California, Davis, CA, USA

    M F Seldin

  4. Department of Genetics and Pathology, University of Uppsala, Uppsala, Sweden

    M E Alarcon-Riquelme

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  1. C M Thorburn
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  2. L Prokunina-Olsson
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  3. K A Sterba
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  4. R F Lum
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  6. M E Alarcon-Riquelme
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  7. L A Criswell
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Correspondence to L A Criswell.

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Thorburn, C., Prokunina-Olsson, L., Sterba, K. et al. Association of PDCD1 genetic variation with risk and clinical manifestations of systemic lupus erythematosus in a multiethnic cohort. Genes Immun 8, 279–287 (2007). https://doi.org/10.1038/sj.gene.6364383

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