Novel genetic markers in the 5 '-flanking region of ANKH are associated with ankylosing spondylitis

F W L Tsui, H W Tsui, E Y Cheng, M Stone, U Payne, J D Reveille, M J Shulman, A D Paterson, R D Inman

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Abstract

Objective. To use a candidate gene approach for the identification of genetic markers that are significantly linked to and associated with ank losing spondylitis (AS). Methods. We searched for novel polymorphisms in the ANKH gene (human homolog of the murine progressive ankylosis gene) and genotyped 2 polymorphic sites, one in the 5'-noncoding region and the other in the promoter region of ANKH, using DNA from affected (n = 273) and unaffected (n = 112) individuals from 124 AS families. We used these ANKH and other nearby polymorphisms to perform linkage and family-based association analyses. Results. We identified 2 novel polymorphic sites: one in the 5'-noncoding region of ANKH involving 1-2 copies of an 8-bp repeat (denoted as ANKH-OR), and the other in the promoter region involving different copy numbers of a triplet repeat (denoted as ANKH-TR). ANKH-OR and ANKH-TR were in complete linkage disequilibrium. Five markers (D5S1953, ANKH-IR, ANKH-OR, D5S1954, and D5S1963) 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; P = 0.015) at the ANKH region. The contribution of ANKH to AS susceptibility (A.) was 1.9. A family-based association study on the same AS families revealed that both ANKH-OR allele 1 and ANKH-TR allele 7 were significantly associated with disease, assuming an additive model (for ANKH-OR allele 1, P = 0.03; for ANKH-TR allele 7, P = 0.04). Conclusion. Our results indicate that ANKH-OR and ANKH-TR are novel genetic markers that are significantly associated with AS.
LanguageEnglish
Pages791-797
Number of pages7
JournalArthritis & Rheumatism
Volume48
Issue number3
DOIs
StatusPublished - 2003

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Spondylitis
5' Flanking Region
Ankylosing Spondylitis
Genetic Markers
Alleles
Genetic Promoter Regions
Trinucleotide Repeats
Ankylosis
Linkage Disequilibrium
Genetic Association Studies
Genes
DNA

Cite this

Tsui, F. W. L., Tsui, H. W., Cheng, E. Y., Stone, M., Payne, U., Reveille, J. D., ... Inman, R. D. (2003). Novel genetic markers in the 5 '-flanking region of ANKH are associated with ankylosing spondylitis. DOI: 10.1002/art.10844

Novel genetic markers in the 5 '-flanking region of ANKH are associated with ankylosing spondylitis. / Tsui, F W L; Tsui, H W; Cheng, E Y; Stone, M; Payne, U; Reveille, J D; Shulman, M J; Paterson, A D; Inman, R D.

In: Arthritis & Rheumatism, Vol. 48, No. 3, 2003, p. 791-797.

Research output: Contribution to journalArticle

Tsui, FWL, Tsui, HW, Cheng, EY, Stone, M, Payne, U, Reveille, JD, Shulman, MJ, Paterson, AD & Inman, RD 2003, 'Novel genetic markers in the 5 '-flanking region of ANKH are associated with ankylosing spondylitis' Arthritis & Rheumatism, vol. 48, no. 3, pp. 791-797. DOI: 10.1002/art.10844
Tsui FWL, Tsui HW, Cheng EY, Stone M, Payne U, Reveille JD et al. Novel genetic markers in the 5 '-flanking region of ANKH are associated with ankylosing spondylitis. Arthritis & Rheumatism. 2003;48(3):791-797. Available from, DOI: 10.1002/art.10844
Tsui, F W L ; Tsui, H W ; Cheng, E Y ; Stone, M ; Payne, U ; Reveille, J D ; Shulman, M J ; Paterson, A D ; Inman, R D. / Novel genetic markers in the 5 '-flanking region of ANKH are associated with ankylosing spondylitis. In: Arthritis & Rheumatism. 2003 ; Vol. 48, No. 3. pp. 791-797
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abstract = "Objective. To use a candidate gene approach for the identification of genetic markers that are significantly linked to and associated with ank losing spondylitis (AS). Methods. We searched for novel polymorphisms in the ANKH gene (human homolog of the murine progressive ankylosis gene) and genotyped 2 polymorphic sites, one in the 5'-noncoding region and the other in the promoter region of ANKH, using DNA from affected (n = 273) and unaffected (n = 112) individuals from 124 AS families. We used these ANKH and other nearby polymorphisms to perform linkage and family-based association analyses. Results. We identified 2 novel polymorphic sites: one in the 5'-noncoding region of ANKH involving 1-2 copies of an 8-bp repeat (denoted as ANKH-OR), and the other in the promoter region involving different copy numbers of a triplet repeat (denoted as ANKH-TR). ANKH-OR and ANKH-TR were in complete linkage disequilibrium. Five markers (D5S1953, ANKH-IR, ANKH-OR, D5S1954, and D5S1963) 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; P = 0.015) at the ANKH region. The contribution of ANKH to AS susceptibility (A.) was 1.9. A family-based association study on the same AS families revealed that both ANKH-OR allele 1 and ANKH-TR allele 7 were significantly associated with disease, assuming an additive model (for ANKH-OR allele 1, P = 0.03; for ANKH-TR allele 7, P = 0.04). Conclusion. Our results indicate that ANKH-OR and ANKH-TR are novel genetic markers that are significantly associated with AS.",
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T1 - Novel genetic markers in the 5 '-flanking region of ANKH are associated with ankylosing spondylitis

AU - Tsui,F W L

AU - Tsui,H W

AU - Cheng,E Y

AU - Stone,M

AU - Payne,U

AU - Reveille,J D

AU - Shulman,M J

AU - Paterson,A D

AU - Inman,R D

N1 - ID number: ISI:000181438800028

PY - 2003

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N2 - Objective. To use a candidate gene approach for the identification of genetic markers that are significantly linked to and associated with ank losing spondylitis (AS). Methods. We searched for novel polymorphisms in the ANKH gene (human homolog of the murine progressive ankylosis gene) and genotyped 2 polymorphic sites, one in the 5'-noncoding region and the other in the promoter region of ANKH, using DNA from affected (n = 273) and unaffected (n = 112) individuals from 124 AS families. We used these ANKH and other nearby polymorphisms to perform linkage and family-based association analyses. Results. We identified 2 novel polymorphic sites: one in the 5'-noncoding region of ANKH involving 1-2 copies of an 8-bp repeat (denoted as ANKH-OR), and the other in the promoter region involving different copy numbers of a triplet repeat (denoted as ANKH-TR). ANKH-OR and ANKH-TR were in complete linkage disequilibrium. Five markers (D5S1953, ANKH-IR, ANKH-OR, D5S1954, and D5S1963) 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; P = 0.015) at the ANKH region. The contribution of ANKH to AS susceptibility (A.) was 1.9. A family-based association study on the same AS families revealed that both ANKH-OR allele 1 and ANKH-TR allele 7 were significantly associated with disease, assuming an additive model (for ANKH-OR allele 1, P = 0.03; for ANKH-TR allele 7, P = 0.04). Conclusion. Our results indicate that ANKH-OR and ANKH-TR are novel genetic markers that are significantly associated with AS.

AB - Objective. To use a candidate gene approach for the identification of genetic markers that are significantly linked to and associated with ank losing spondylitis (AS). Methods. We searched for novel polymorphisms in the ANKH gene (human homolog of the murine progressive ankylosis gene) and genotyped 2 polymorphic sites, one in the 5'-noncoding region and the other in the promoter region of ANKH, using DNA from affected (n = 273) and unaffected (n = 112) individuals from 124 AS families. We used these ANKH and other nearby polymorphisms to perform linkage and family-based association analyses. Results. We identified 2 novel polymorphic sites: one in the 5'-noncoding region of ANKH involving 1-2 copies of an 8-bp repeat (denoted as ANKH-OR), and the other in the promoter region involving different copy numbers of a triplet repeat (denoted as ANKH-TR). ANKH-OR and ANKH-TR were in complete linkage disequilibrium. Five markers (D5S1953, ANKH-IR, ANKH-OR, D5S1954, and D5S1963) 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; P = 0.015) at the ANKH region. The contribution of ANKH to AS susceptibility (A.) was 1.9. A family-based association study on the same AS families revealed that both ANKH-OR allele 1 and ANKH-TR allele 7 were significantly associated with disease, assuming an additive model (for ANKH-OR allele 1, P = 0.03; for ANKH-TR allele 7, P = 0.04). Conclusion. Our results indicate that ANKH-OR and ANKH-TR are novel genetic markers that are significantly associated with AS.

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DO - 10.1002/art.10844

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JO - Arthritis & Rheumatism

T2 - Arthritis & Rheumatism

JF - Arthritis & Rheumatism

SN - 0004-3591

IS - 3

ER -