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Association tests with systemic lupus erythematosus (SLE) of IL10 markers indicate a direct involvement of a CA repeat in the 5′ regulatory region

Genes & Immunity volume 3, pages 454–463 (2002)Cite this article

Abstract

Many lines of evidence suggest that IL10 is a strong candidate gene for systemic lupus erythematosus (SLE) susceptibility. In our previously reported study an allele (IL10.G-140bp) of the microsatellite IL10.G located at position −1100 was significantly increased in Italian SLE patients in comparison with controls. Starting from this observation, we tested if sequence variations in the vicinity of IL10.G were more strongly associated with SLE. We performed a comprehensive association study including 26 SNPs (of which four were newly identified in the present study by DHPLC analysis) spanning 8.5 Kb of the 5′ flanking and the transcribed region of the IL10 gene. The association study was performed by the DNA pool method on an extended panel of Italian patients (205) and controls (631). Haplotypic associations were studied by individual typing of seven selected markers surrounding IL10.G. Gene, genotype and haplotype frequencies were not significantly different in patients and controls. Thus the IL10.G microsatellite remains to date the only IL10 marker associated with SLE in our population. A meta-analysis of all published results indicates a possible direct role of the IL10.G repeat number in SLE susceptibiliy.

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Acknowledgements

This work was supported by Telethon grant E1221 and by Eastern Piedmont University (fondi ex 60%). Marta Mellai is a PhD student in Molecular Medicine. The authors are grateful to Dr Roberto Tosi for critically reading the manuscript, and to Dr Dieter Kube for sending reference DNA samples to set typing conditions for SNPs of the distal IL10 5′ flanking region.

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Authors and Affiliations

  1. Dipartimento Scienze Mediche, Laboratorio di Genetica Umana, and IRCAD, Università del Piemonte Orientale, Novara, Italy

    S D' Alfonso, M Giordano, M Mellai, M Lanceni, N Barizzone & P Momigliano-Richiardi

  2. Unità di Immunologia Clinica e Allergologia, IRCCS Ospedale Maggiore and Università di Milano, Milano, Italy

    M Marchini & R Scorza

  3. Istituto di Clinica Medica, Ematologia ed Immunologia Clinica, Università di Ancona, Italy

    M G Danieli & M Cappelli

  4. Unita' di Reumatologia e Immunologia Clinica, Universita' Vita e Salute, IRCCS Ospedale San Raffaele, Milano, Italy

    P Rovere & M G Sabbadini

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Correspondence to S D' Alfonso.

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D' Alfonso, S., Giordano, M., Mellai, M. et al. Association tests with systemic lupus erythematosus (SLE) of IL10 markers indicate a direct involvement of a CA repeat in the 5′ regulatory region. Genes Immun 3, 454–463 (2002). https://doi.org/10.1038/sj.gene.6363928

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