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Peptidoglycan recognition proteins Pglyrp3 and Pglyrp4 are encoded from the epidermal differentiation complex and are candidate genes for the Psors4 locus on chromosome 1q21

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Abstract

Psoriasis is a common inflammatory skin disease caused by genetic and environmental factors, including bacterial and viral infections. Since the skin is in constant contact with commensal and pathogenic microorganisms, we examined well-supported psoriasis genetic linkage intervals to identify genes encoding innate immune pattern recognition proteins that may play a role in pathogenesis. Two peptidoglycan recognition proteins, Pglyrp3 and Pglyrp4, are localized to the Psors4 locus on chromosome 1q21 in a gene cluster known as the epidermal differentiation complex (EDC). We show that these genes are expressed in the skin as well as in germinal centers in the tonsil. We tested 13 SNPs in or near these genes for association with psoriasis in two independent patient collections: a family-based patient set comprised of 375 individuals from 101 families, and a case–control patient collection of 282 patients with moderate to severe psoriasis and 192 healthy controls. In the family-based analysis, several SNPs in the Pglyrp3–Pglyrp4 locus show association with psoriasis (0.01<P<0.05). Multiple-SNP haplotypes incorporating Pglyrp3 and Pglyrp4 SNPs also show significant association in the transmission disequilibrium test (TDT; P<0.01). In the case–control test, none of the SNPs that we tested show association with psoriasis when analyzed in single-SNP or haplotype-based tests. The discordance between the TDT and case–control results suggests that the two populations are significantly different in disease etiology, that the polymorphism responsible for the Psors4 linkage is elsewhere in the Pglyrp locus, or that the causative Psors4 polymorphism is in a location near but not in the Pglyrp locus. These data are consistent with previous reports of association of psoriasis with genes on 1q21, and suggest a role for Pglyrps in skin biology.

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Acknowledgements

We thank all of the patients who donated their DNA to this study, and the National Psoriasis Foundation for providing some of the nuclear families for the family-based analysis. We also thank Brittney Coleman, Michele McAuliffe and Chris Tonkin for DNA sequencing, Xiamei Zhang for technical assistance and Herman Van Vlijmen for homology modeling of Pglyrp3 and Pglyrp4.

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Authors and Affiliations

  1. Department of Genetics, BiogenIdec, Inc, 12 Cambridge Center, Cambridge, MA, 02142, USA

    Chao Sun, Punam Mathur & John Carulli

  2. Department of Discovery Biology, BiogenIdec, Inc., 12 Cambridge Center, Cambridge, MA, 02142, USA

    Rich Tizard

  3. Department of Medical Research, BiogenIdec, Inc., 12 Cambridge Center, Cambridge, MA, 02142, USA

    Barry Ticho

  4. Department of Research Pathology, BiogenIdec, Inc., 12 Cambridge Center, Cambridge, MA, 02142, USA

    Tom Crowell & Humphrey Gardner

  5. Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA

    Josée Dupuis

  6. Department of Genetics and Division of Dermatology, Department of Medicine, Washington University School of Medicine, 8232, 4566 Scott Avenue, St. Louis, MO, 63110, USA

    Anne M. Bowcock

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  1. Chao Sun
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Correspondence to John Carulli.

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Sun, C., Mathur, P., Dupuis, J. et al. Peptidoglycan recognition proteins Pglyrp3 and Pglyrp4 are encoded from the epidermal differentiation complex and are candidate genes for the Psors4 locus on chromosome 1q21. Hum Genet 119, 113–125 (2006). https://doi.org/10.1007/s00439-005-0115-8

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