• Medientyp: E-Artikel
  • Titel: Novel genetic markers in the 5′‐flanking region of ANKH are associated with ankylosing spondylitis
  • Beteiligte: Tsui, Florence W. L.; Tsui, Hing Wo; Cheng, Emily Y.; Stone, Millicent; Payne, Ursula; Reveille, John D.; Shulman, Marc J.; Paterson, Andrew D.; Inman, Robert D.
  • Erschienen: Wiley, 2003
  • Erschienen in: Arthritis & Rheumatism
  • Umfang: 791-797
  • Sprache: Englisch
  • DOI: 10.1002/art.10844
  • ISSN: 1529-0131; 0004-3591
  • Schlagwörter: Pharmacology (medical) ; Immunology ; Rheumatology ; Immunology and Allergy
  • Zusammenfassung: <jats:title>Abstract</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>To use a candidate gene approach for the identification of genetic markers that are significantly linked to and associated with ankylosing spondylitis (AS).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We searched for novel polymorphisms in the <jats:italic>ANKH</jats:italic> gene (human homolog of the murine <jats:italic>progressive ankylosis</jats:italic> gene) and genotyped 2 polymorphic sites, one in the 5′‐noncoding region and the other in the promoter region of <jats:italic>ANKH</jats:italic>, using DNA from affected (n = 273) and unaffected (n = 112) individuals from 124 AS families. We used these <jats:italic>ANKH</jats:italic> and other nearby polymorphisms to perform linkage and family‐based association analyses.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We identified 2 novel polymorphic sites: one in the 5′‐noncoding region of <jats:italic>ANKH</jats:italic> involving 1–2 copies of an 8‐bp repeat (denoted as <jats:italic>ANKH‐OR</jats:italic>), and the other in the promoter region involving different copy numbers of a triplet repeat (denoted as <jats:italic>ANKH‐TR</jats:italic>). <jats:italic>ANKH‐OR</jats:italic> and <jats:italic>ANKH‐TR</jats:italic> were in complete linkage disequilibrium. Five markers (<jats:italic>D5S1953</jats:italic>, <jats:italic>ANKH‐TR</jats:italic>, <jats:italic>ANKH‐OR</jats:italic>, <jats:italic>D5S1954</jats:italic>, and <jats:italic>D5S1963</jats:italic>) were used for both the linkage and association analyses. Multipoint linkage analysis of 124 AS families showed a modest level of significance (nonparametric linkage score 2.15; <jats:italic>P</jats:italic> = 0.015) at the <jats:italic>ANKH</jats:italic> region. The contribution of <jats:italic>ANKH</jats:italic> to AS susceptibility (λ<jats:sub>s</jats:sub>) was 1.9. A family‐based association study on the same AS families revealed that both <jats:italic>ANKH‐OR</jats:italic> allele 1 and <jats:italic>ANKH‐TR</jats:italic> allele 7 were significantly associated with disease, assuming an additive model (for <jats:italic>ANKH‐OR</jats:italic> allele 1, <jats:italic>P</jats:italic> = 0.03; for <jats:italic>ANKH‐TR</jats:italic> allele 7, <jats:italic>P</jats:italic> = 0.04).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Our results indicate that <jats:italic>ANKH‐OR</jats:italic> and <jats:italic>ANKH‐TR</jats:italic> are novel genetic markers that are significantly associated with AS.</jats:p></jats:sec>
  • Beschreibung: <jats:title>Abstract</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>To use a candidate gene approach for the identification of genetic markers that are significantly linked to and associated with ankylosing spondylitis (AS).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We searched for novel polymorphisms in the <jats:italic>ANKH</jats:italic> gene (human homolog of the murine <jats:italic>progressive ankylosis</jats:italic> gene) and genotyped 2 polymorphic sites, one in the 5′‐noncoding region and the other in the promoter region of <jats:italic>ANKH</jats:italic>, using DNA from affected (n = 273) and unaffected (n = 112) individuals from 124 AS families. We used these <jats:italic>ANKH</jats:italic> and other nearby polymorphisms to perform linkage and family‐based association analyses.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We identified 2 novel polymorphic sites: one in the 5′‐noncoding region of <jats:italic>ANKH</jats:italic> involving 1–2 copies of an 8‐bp repeat (denoted as <jats:italic>ANKH‐OR</jats:italic>), and the other in the promoter region involving different copy numbers of a triplet repeat (denoted as <jats:italic>ANKH‐TR</jats:italic>). <jats:italic>ANKH‐OR</jats:italic> and <jats:italic>ANKH‐TR</jats:italic> were in complete linkage disequilibrium. Five markers (<jats:italic>D5S1953</jats:italic>, <jats:italic>ANKH‐TR</jats:italic>, <jats:italic>ANKH‐OR</jats:italic>, <jats:italic>D5S1954</jats:italic>, and <jats:italic>D5S1963</jats:italic>) were used for both the linkage and association analyses. Multipoint linkage analysis of 124 AS families showed a modest level of significance (nonparametric linkage score 2.15; <jats:italic>P</jats:italic> = 0.015) at the <jats:italic>ANKH</jats:italic> region. The contribution of <jats:italic>ANKH</jats:italic> to AS susceptibility (λ<jats:sub>s</jats:sub>) was 1.9. A family‐based association study on the same AS families revealed that both <jats:italic>ANKH‐OR</jats:italic> allele 1 and <jats:italic>ANKH‐TR</jats:italic> allele 7 were significantly associated with disease, assuming an additive model (for <jats:italic>ANKH‐OR</jats:italic> allele 1, <jats:italic>P</jats:italic> = 0.03; for <jats:italic>ANKH‐TR</jats:italic> allele 7, <jats:italic>P</jats:italic> = 0.04).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Our results indicate that <jats:italic>ANKH‐OR</jats:italic> and <jats:italic>ANKH‐TR</jats:italic> are novel genetic markers that are significantly associated with AS.</jats:p></jats:sec>
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