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Evaluation of microsatellite markers in association studies: a search for an immune-related susceptibility gene in sarcoidosis

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Abstract

Association studies using linkage disequilibrium (LD) between candidate loci and nearby markers have been proposed to identify susceptibility genes for complex diseases. We analyzed polymorphisms of microsatellites (MSs) and LD patterns of the regions in which candidate genes related to the Th1 immune response have been annotated and attempted to identify a susceptibility gene for sarcoidosis in a marker-based association study. Nineteen MSs were identified in six Th1-related genes (IFNGR1, IFNGR2, IL12RB1, IL12RB2, STAT1 and STAT4) and then eight were further characterized as useful polymorphic markers. Most of these MSs showed LD with single nucleotide polymorphisms (SNPs) on both 5′ and 3′ ends of these candidate genes, in which r2 values between at least one of the MS marker alleles and the SNPs were higher than 0.1. A significant association with one MS allele near STAT4 was shown and a cluster of SNPs in LD with the MS marker was associated with sarcoidosis. These results suggest that association studies using not only SNPs but also multi-allelic MS within or near candidate loci would be useful markers to search for a disease susceptibility gene, especially in populations with unknown LD structure.

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Acknowledgements

The authors thank Shizu Hayashi (The James Hogg iCAPTURE Centre for cardiovascular and pulmonary research, Vancouver, BC, Canada) for her critical reading of this manuscript and Kazuko Tanabe (Research Institute, International Medical Center of Japan, Tokyo, Japan) for her helpful suggestions. This work was supported in part by research grants for Research on Human Genome, Tissue Engineering Food Biotechnology from the Ministry of Health Labour and Welfare of Japan and by the Organization for Pharmaceutical Safety and Research in 2002 and 2003

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Authors and Affiliations

  1. Department of Respiratory Diseases, Research Institute, International Medical Center of Japan, Tokyo, 162-8655, Japan

    Goh Tanaka, Ikumi Matsushita, Minako Hijikata & Naoto Keicho

  2. Department of Respiratory Diseases, University of Tokyo, Tokyo, 113-8655, Japan

    Goh Tanaka & Taiji Nagata

  3. Department of Human Genetics, Graduate School of Medicine, University of Tokyo, Tokyo, 113-8655, Japan

    Jun Ohashi, Naoyuki Tsuchiya & Katsushi Tokunaga

  4. Department of Respiratory Diseases, Japanese Red Cross Medical Center, Tokyo, 150-8935, Japan

    Soichiro Ikushima & Masaru Oritsu

  5. Department of Allergy and Rheumatology, University of Tokyo, Tokyo, 113-8655, Japan

    Kazuhiko Yamamoto

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  1. Goh Tanaka
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Correspondence to Naoto Keicho.

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Tanaka, G., Matsushita, I., Ohashi, J. et al. Evaluation of microsatellite markers in association studies: a search for an immune-related susceptibility gene in sarcoidosis. Immunogenetics 56, 861–870 (2005). https://doi.org/10.1007/s00251-004-0753-3

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  • DOI: https://doi.org/10.1007/s00251-004-0753-3

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