Evaluation of TRAF6 in a large multiancestral lupus cohort
Objective Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with significant immune system aberrations resulting from complex heritable genetics as well as environmental factors. We undertook to study the role of TRAF6 as a candidate gene for SLE, since it plays a major role i...
| Autores Principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | Artículo (Article) |
| Lenguaje: | Inglés (English) |
| Publicado: |
2012
|
| Materias: | |
| Acceso en línea: | https://repository.urosario.edu.co/handle/10336/22999 https://doi.org/10.1002/art.34361 |
| id |
ir-10336-22999 |
|---|---|
| recordtype |
dspace |
| spelling |
ir-10336-229992022-05-02T12:37:14Z Evaluation of TRAF6 in a large multiancestral lupus cohort Namjou, Bahram Choi, Chan?Bum Harley, Isaac T. W. Alarcón?Riquelme, Marta E. Kelly, Jennifer A. Glenn, Stuart B. Ojwang, Joshua O. Adler, Adam Kim, Kwangwoo Gallant, Caroline J. Boackle, Susan A. Criswell, Lindsey A. Kimberly, Robert P. Brown, Elizabeth E. Edberg, Jeffrey Alarcón, Graciela S. Stevens, Anne M. Jacob, Chaim O. Gilkeson, Gary S. Kamen, Diane L. Tsao, Betty P. Kim, Eun?Mi Park, So?Yeon Sung, Yoon?Kyoung Guthridge, Joel M. Merrill, Joan T. Petri, Michelle Ramsey?Goldman, Rosalind Vilá, Luis M. Niewold, Timothy B. Martin, Javier Pons?Estel, Bernardo A. Vyse, Timothy J. Freedman, Barry I. Moser, Kathy L. Gaffney, Patrick M. Williams, Adrienne H. Comeau, Mary E. Reveille, John D. Kang, Changwon James, Judith A. Scofield, R. Hal Langefeld, Carl D. Kaufman, Kenneth M. Harley, John B. Bae, Sang?Cheol Anaya, Juan-Manuel Tumor necrosis factor receptor associated factor 6 African american Article Calculation Controlled study Ethnicity Female Gene linkage disequilibrium Genetic association Genetic heterogeneity Genotype Heredity Human Immunity Immunopathogenesis Major clinical study Male Meta analysis (topic) Organogenesis Pedigree analysis Population based case control study Priority journal Rheumatoid arthritis Signal transduction Single nucleotide polymorphism Systemic lupus erythematosus Thrombocytopenia Alleles Case-control studies Cohort studies Female Gene frequency Genetic association studies Genetic predisposition to disease Genotype Haplotypes Humans Male Tnf receptor-associated factor 6 systemic single nucleotide Lupus erythematosus Polymorphism Objective Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with significant immune system aberrations resulting from complex heritable genetics as well as environmental factors. We undertook to study the role of TRAF6 as a candidate gene for SLE, since it plays a major role in several signaling pathways that are important for immunity and organ development. Methods Fifteen single-nucleotide polymorphisms (SNPs) across TRAF6 were evaluated in 7,490 SLE patients and 6,780 control subjects from different ancestries. Population-based case-control association analyses and meta-analyses were performed. P values, false discovery rate q values, and odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. Results Evidence of associations was detected in multiple SNPs. The best overall P values were obtained for SNPs rs5030437 and rs4755453 (P = 7.85 × 10 -5 and P = 4.73 × 10 -5, respectively) without significant heterogeneity among populations (P = 0.67 and P = 0.50, respectively, in Q statistic). In addition, SNP rs540386, which was previously reported to be associated with rheumatoid arthritis (RA), was found to be in linkage disequilibrium with these 2 SNPs (r 2 = 0.95) and demonstrated evidence of association with SLE in the same direction (meta-analysis P = 9.15 × 10 -4, OR 0.89 [95% CI 0.83-0.95]). The presence of thrombocytopenia improved the overall results in different populations (meta-analysis P = 1.99 × 10 -6, OR 0.57 [95% CI 0.45-0.72], for rs5030470). Finally, evidence of family-based association in 34 African American pedigrees with the presence of thrombocytopenia was detected in 1 available SNP (rs5030437) with a Z score magnitude of 2.28 (P = 0.02) under a dominant model. Conclusion Our data indicate the presence of association of TRAF6 with SLE, consistent with the previous report of association with RA. These data provide further support for the involvement of TRAF6 in the pathogenesis of autoimmunity. Copyright © 2012 by the American College of Rheumatology. 2012 2020-05-25T23:59:11Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion https://repository.urosario.edu.co/handle/10336/22999 https://doi.org/10.1002/art.34361 eng info:eu-repo/semantics/openAccess application/pdf instname:Universidad del Rosario |
| institution |
EdocUR - Universidad del Rosario |
| collection |
DSpace |
| language |
Inglés (English) |
| topic |
Tumor necrosis factor receptor associated factor 6 African american Article Calculation Controlled study Ethnicity Female Gene linkage disequilibrium Genetic association Genetic heterogeneity Genotype Heredity Human Immunity Immunopathogenesis Major clinical study Male Meta analysis (topic) Organogenesis Pedigree analysis Population based case control study Priority journal Rheumatoid arthritis Signal transduction Single nucleotide polymorphism Systemic lupus erythematosus Thrombocytopenia Alleles Case-control studies Cohort studies Female Gene frequency Genetic association studies Genetic predisposition to disease Genotype Haplotypes Humans Male Tnf receptor-associated factor 6 systemic single nucleotide Lupus erythematosus Polymorphism |
| spellingShingle |
Tumor necrosis factor receptor associated factor 6 African american Article Calculation Controlled study Ethnicity Female Gene linkage disequilibrium Genetic association Genetic heterogeneity Genotype Heredity Human Immunity Immunopathogenesis Major clinical study Male Meta analysis (topic) Organogenesis Pedigree analysis Population based case control study Priority journal Rheumatoid arthritis Signal transduction Single nucleotide polymorphism Systemic lupus erythematosus Thrombocytopenia Alleles Case-control studies Cohort studies Female Gene frequency Genetic association studies Genetic predisposition to disease Genotype Haplotypes Humans Male Tnf receptor-associated factor 6 systemic single nucleotide Lupus erythematosus Polymorphism Namjou, Bahram Choi, Chan?Bum Harley, Isaac T. W. Alarcón?Riquelme, Marta E. Kelly, Jennifer A. Glenn, Stuart B. Ojwang, Joshua O. Adler, Adam Kim, Kwangwoo Gallant, Caroline J. Boackle, Susan A. Criswell, Lindsey A. Kimberly, Robert P. Brown, Elizabeth E. Edberg, Jeffrey Alarcón, Graciela S. Stevens, Anne M. Jacob, Chaim O. Gilkeson, Gary S. Kamen, Diane L. Tsao, Betty P. Kim, Eun?Mi Park, So?Yeon Sung, Yoon?Kyoung Guthridge, Joel M. Merrill, Joan T. Petri, Michelle Ramsey?Goldman, Rosalind Vilá, Luis M. Niewold, Timothy B. Martin, Javier Pons?Estel, Bernardo A. Vyse, Timothy J. Freedman, Barry I. Moser, Kathy L. Gaffney, Patrick M. Williams, Adrienne H. Comeau, Mary E. Reveille, John D. Kang, Changwon James, Judith A. Scofield, R. Hal Langefeld, Carl D. Kaufman, Kenneth M. Harley, John B. Bae, Sang?Cheol Anaya, Juan-Manuel Evaluation of TRAF6 in a large multiancestral lupus cohort |
| description |
Objective Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with significant immune system aberrations resulting from complex heritable genetics as well as environmental factors. We undertook to study the role of TRAF6 as a candidate gene for SLE, since it plays a major role in several signaling pathways that are important for immunity and organ development. Methods Fifteen single-nucleotide polymorphisms (SNPs) across TRAF6 were evaluated in 7,490 SLE patients and 6,780 control subjects from different ancestries. Population-based case-control association analyses and meta-analyses were performed. P values, false discovery rate q values, and odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. Results Evidence of associations was detected in multiple SNPs. The best overall P values were obtained for SNPs rs5030437 and rs4755453 (P = 7.85 × 10 -5 and P = 4.73 × 10 -5, respectively) without significant heterogeneity among populations (P = 0.67 and P = 0.50, respectively, in Q statistic). In addition, SNP rs540386, which was previously reported to be associated with rheumatoid arthritis (RA), was found to be in linkage disequilibrium with these 2 SNPs (r 2 = 0.95) and demonstrated evidence of association with SLE in the same direction (meta-analysis P = 9.15 × 10 -4, OR 0.89 [95% CI 0.83-0.95]). The presence of thrombocytopenia improved the overall results in different populations (meta-analysis P = 1.99 × 10 -6, OR 0.57 [95% CI 0.45-0.72], for rs5030470). Finally, evidence of family-based association in 34 African American pedigrees with the presence of thrombocytopenia was detected in 1 available SNP (rs5030437) with a Z score magnitude of 2.28 (P = 0.02) under a dominant model. Conclusion Our data indicate the presence of association of TRAF6 with SLE, consistent with the previous report of association with RA. These data provide further support for the involvement of TRAF6 in the pathogenesis of autoimmunity. Copyright © 2012 by the American College of Rheumatology. |
| format |
Artículo (Article) |
| author |
Namjou, Bahram Choi, Chan?Bum Harley, Isaac T. W. Alarcón?Riquelme, Marta E. Kelly, Jennifer A. Glenn, Stuart B. Ojwang, Joshua O. Adler, Adam Kim, Kwangwoo Gallant, Caroline J. Boackle, Susan A. Criswell, Lindsey A. Kimberly, Robert P. Brown, Elizabeth E. Edberg, Jeffrey Alarcón, Graciela S. Stevens, Anne M. Jacob, Chaim O. Gilkeson, Gary S. Kamen, Diane L. Tsao, Betty P. Kim, Eun?Mi Park, So?Yeon Sung, Yoon?Kyoung Guthridge, Joel M. Merrill, Joan T. Petri, Michelle Ramsey?Goldman, Rosalind Vilá, Luis M. Niewold, Timothy B. Martin, Javier Pons?Estel, Bernardo A. Vyse, Timothy J. Freedman, Barry I. Moser, Kathy L. Gaffney, Patrick M. Williams, Adrienne H. Comeau, Mary E. Reveille, John D. Kang, Changwon James, Judith A. Scofield, R. Hal Langefeld, Carl D. Kaufman, Kenneth M. Harley, John B. Bae, Sang?Cheol Anaya, Juan-Manuel |
| author_facet |
Namjou, Bahram Choi, Chan?Bum Harley, Isaac T. W. Alarcón?Riquelme, Marta E. Kelly, Jennifer A. Glenn, Stuart B. Ojwang, Joshua O. Adler, Adam Kim, Kwangwoo Gallant, Caroline J. Boackle, Susan A. Criswell, Lindsey A. Kimberly, Robert P. Brown, Elizabeth E. Edberg, Jeffrey Alarcón, Graciela S. Stevens, Anne M. Jacob, Chaim O. Gilkeson, Gary S. Kamen, Diane L. Tsao, Betty P. Kim, Eun?Mi Park, So?Yeon Sung, Yoon?Kyoung Guthridge, Joel M. Merrill, Joan T. Petri, Michelle Ramsey?Goldman, Rosalind Vilá, Luis M. Niewold, Timothy B. Martin, Javier Pons?Estel, Bernardo A. Vyse, Timothy J. Freedman, Barry I. Moser, Kathy L. Gaffney, Patrick M. Williams, Adrienne H. Comeau, Mary E. Reveille, John D. Kang, Changwon James, Judith A. Scofield, R. Hal Langefeld, Carl D. Kaufman, Kenneth M. Harley, John B. Bae, Sang?Cheol Anaya, Juan-Manuel |
| author_sort |
Namjou, Bahram |
| title |
Evaluation of TRAF6 in a large multiancestral lupus cohort |
| title_short |
Evaluation of TRAF6 in a large multiancestral lupus cohort |
| title_full |
Evaluation of TRAF6 in a large multiancestral lupus cohort |
| title_fullStr |
Evaluation of TRAF6 in a large multiancestral lupus cohort |
| title_full_unstemmed |
Evaluation of TRAF6 in a large multiancestral lupus cohort |
| title_sort |
evaluation of traf6 in a large multiancestral lupus cohort |
| publishDate |
2012 |
| url |
https://repository.urosario.edu.co/handle/10336/22999 https://doi.org/10.1002/art.34361 |
| _version_ |
1740172831086346240 |
| score |
12,131701 |