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ANKH variants associated with ankylosing spondylitis: gender differences
The ank (progressive ankylosis) mutant mouse, which has a nonsense mutation in exon 12 of the inorganic pyrophosphate regulator gene (ank), exhibits aberrant joint ankylosis similar to human ankylosing spondylitis (AS). We previously performed family-based association analyses of 124 Caucasian AS fa...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2005
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1174945/ https://www.ncbi.nlm.nih.gov/pubmed/15899038 http://dx.doi.org/10.1186/ar1701 |
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author | Tsui, Hing Wo Inman, Robert D Paterson, Andrew D Reveille, John D Tsui, Florence WL |
author_facet | Tsui, Hing Wo Inman, Robert D Paterson, Andrew D Reveille, John D Tsui, Florence WL |
author_sort | Tsui, Hing Wo |
collection | PubMed |
description | The ank (progressive ankylosis) mutant mouse, which has a nonsense mutation in exon 12 of the inorganic pyrophosphate regulator gene (ank), exhibits aberrant joint ankylosis similar to human ankylosing spondylitis (AS). We previously performed family-based association analyses of 124 Caucasian AS families and showed that novel genetic markers in the 5' flanking region of ANKH (the human homolog of the murine ank gene) are modestly associated with AS. The objective of the present study was to conduct a more extensive evaluation of ANKH variants that are significantly associated with AS and to determine whether the association is gender specific. We genotyped 201 multiplex AS families with nine ANKH intragenetic and two flanking microsatellite markers, and performed family-based association analyses. We showed that ANKH variants located in two different regions of the ANKH gene were associated with AS. Results of haplotype analyses indicated that, after Bonferroni correction, the haplotype combination of rs26307 [C] and rs27356 [C] is significantly associated with AS in men (recessive/dominant model; P = 0.004), and the haplotype combination of rs28006 [C] and rs25957 [C] is significantly associated with AS in women (recessive/dominant model; P = 0.004). A test of interaction identified rs26307 (i.e. the region that was associated in men with AS) as showing a difference in the strength of the association by gender. The region associated with AS in women only showed significance in the test of interaction among the subset of families with affected individuals of both genders. These findings support the concept that ANKH plays a role in genetic susceptibility to AS and reveals a gender–genotype specificity in this interaction. |
format | Text |
id | pubmed-1174945 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2005 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-11749452005-07-13 ANKH variants associated with ankylosing spondylitis: gender differences Tsui, Hing Wo Inman, Robert D Paterson, Andrew D Reveille, John D Tsui, Florence WL Arthritis Res Ther Research Article The ank (progressive ankylosis) mutant mouse, which has a nonsense mutation in exon 12 of the inorganic pyrophosphate regulator gene (ank), exhibits aberrant joint ankylosis similar to human ankylosing spondylitis (AS). We previously performed family-based association analyses of 124 Caucasian AS families and showed that novel genetic markers in the 5' flanking region of ANKH (the human homolog of the murine ank gene) are modestly associated with AS. The objective of the present study was to conduct a more extensive evaluation of ANKH variants that are significantly associated with AS and to determine whether the association is gender specific. We genotyped 201 multiplex AS families with nine ANKH intragenetic and two flanking microsatellite markers, and performed family-based association analyses. We showed that ANKH variants located in two different regions of the ANKH gene were associated with AS. Results of haplotype analyses indicated that, after Bonferroni correction, the haplotype combination of rs26307 [C] and rs27356 [C] is significantly associated with AS in men (recessive/dominant model; P = 0.004), and the haplotype combination of rs28006 [C] and rs25957 [C] is significantly associated with AS in women (recessive/dominant model; P = 0.004). A test of interaction identified rs26307 (i.e. the region that was associated in men with AS) as showing a difference in the strength of the association by gender. The region associated with AS in women only showed significance in the test of interaction among the subset of families with affected individuals of both genders. These findings support the concept that ANKH plays a role in genetic susceptibility to AS and reveals a gender–genotype specificity in this interaction. BioMed Central 2005 2005-02-25 /pmc/articles/PMC1174945/ /pubmed/15899038 http://dx.doi.org/10.1186/ar1701 Text en Copyright © 2005 Tsui et al.; licensee BioMed Central Ltd. |
spellingShingle | Research Article Tsui, Hing Wo Inman, Robert D Paterson, Andrew D Reveille, John D Tsui, Florence WL ANKH variants associated with ankylosing spondylitis: gender differences |
title | ANKH variants associated with ankylosing spondylitis: gender differences |
title_full | ANKH variants associated with ankylosing spondylitis: gender differences |
title_fullStr | ANKH variants associated with ankylosing spondylitis: gender differences |
title_full_unstemmed | ANKH variants associated with ankylosing spondylitis: gender differences |
title_short | ANKH variants associated with ankylosing spondylitis: gender differences |
title_sort | ankh variants associated with ankylosing spondylitis: gender differences |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1174945/ https://www.ncbi.nlm.nih.gov/pubmed/15899038 http://dx.doi.org/10.1186/ar1701 |
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