HLA–DPB1 and DPB2 are genetic loci for systemic sclerosis: A genome‐wide association study in Koreans with replication in North Americans
Objective To identify systemic sclerosis (SSc) susceptibility loci via a genome‐wide association study. Methods A genome‐wide association study was performed in 137 patients with SSc and 564 controls from Korea using the Affymetrix Human SNP Array 5.0. After fine‐mapping studies, the results were re...
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| Published in | Arthritis and rheumatism Vol. 60; no. 12; pp. 3807 - 3814 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
01.12.2009
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0004-3591 1529-0131 1529-0131 |
| DOI | 10.1002/art.24982 |
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| Abstract | Objective
To identify systemic sclerosis (SSc) susceptibility loci via a genome‐wide association study.
Methods
A genome‐wide association study was performed in 137 patients with SSc and 564 controls from Korea using the Affymetrix Human SNP Array 5.0. After fine‐mapping studies, the results were replicated in 1,107 SSc patients and 2,747 controls from a US Caucasian population.
Results
The single‐nucleotide polymorphisms (SNPs) (rs3128930, rs7763822, rs7764491, rs3117230, and rs3128965) of HLA–DPB1 and DPB2 on chromosome 6 formed a distinctive peak with log P values for association with SSc susceptibility (P = 8.16 × 10−13). Subtyping analysis of HLA–DPB1 showed that DPB1*1301 (P = 7.61 × 10−8) and DPB1*0901 (P = 2.55 × 10−5) were the subtypes most susceptible to SSc in Korean subjects. In US Caucasians, 2 pairs of SNPs, rs7763822/rs7764491 and rs3117230/rs3128965, showed strong association with SSc patients who had either circulating anti–DNA topoisomerase I (P = 7.58 × 10−17/4.84 × 10−16) or anticentromere autoantibodies (P = 1.12 × 10−3/3.2 × 10−5), respectively.
Conclusion
The results of our genome‐wide association study in Korean subjects indicate that the region of HLA–DPB1 and DPB2 contains the loci most susceptible to SSc in a Korean population. The confirmatory studies in US Caucasians indicate that specific SNPs of HLA–DPB1 and/or DPB2 are strongly associated with US Caucasian patients with SSc who are positive for anti–DNA topoisomerase I or anticentromere autoantibodies. |
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| AbstractList | To identify systemic sclerosis (SSc) susceptibility loci via a genome-wide association study.
A genome-wide association study was performed in 137 patients with SSc and 564 controls from Korea using the Affymetrix Human SNP Array 5.0. After fine-mapping studies, the results were replicated in 1,107 SSc patients and 2,747 controls from a US Caucasian population.
The single-nucleotide polymorphisms (SNPs) (rs3128930, rs7763822, rs7764491, rs3117230, and rs3128965) of HLA-DPB1 and DPB2 on chromosome 6 formed a distinctive peak with log P values for association with SSc susceptibility (P=8.16x10(-13)). Subtyping analysis of HLA-DPB1 showed that DPB1*1301 (P=7.61x10(-8)) and DPB1*0901 (P=2.55x10(-5)) were the subtypes most susceptible to SSc in Korean subjects. In US Caucasians, 2 pairs of SNPs, rs7763822/rs7764491 and rs3117230/rs3128965, showed strong association with SSc patients who had either circulating anti-DNA topoisomerase I (P=7.58x10(-17)/4.84x10(-16)) or anticentromere autoantibodies (P=1.12x10(-3)/3.2x10(-5)), respectively.
The results of our genome-wide association study in Korean subjects indicate that the region of HLA-DPB1 and DPB2 contains the loci most susceptible to SSc in a Korean population. The confirmatory studies in US Caucasians indicate that specific SNPs of HLA-DPB1 and/or DPB2 are strongly associated with US Caucasian patients with SSc who are positive for anti-DNA topoisomerase I or anticentromere autoantibodies. To identify systemic sclerosis (SSc) susceptibility loci via a genome-wide association study.OBJECTIVETo identify systemic sclerosis (SSc) susceptibility loci via a genome-wide association study.A genome-wide association study was performed in 137 patients with SSc and 564 controls from Korea using the Affymetrix Human SNP Array 5.0. After fine-mapping studies, the results were replicated in 1,107 SSc patients and 2,747 controls from a US Caucasian population.METHODSA genome-wide association study was performed in 137 patients with SSc and 564 controls from Korea using the Affymetrix Human SNP Array 5.0. After fine-mapping studies, the results were replicated in 1,107 SSc patients and 2,747 controls from a US Caucasian population.The single-nucleotide polymorphisms (SNPs) (rs3128930, rs7763822, rs7764491, rs3117230, and rs3128965) of HLA-DPB1 and DPB2 on chromosome 6 formed a distinctive peak with log P values for association with SSc susceptibility (P=8.16x10(-13)). Subtyping analysis of HLA-DPB1 showed that DPB1*1301 (P=7.61x10(-8)) and DPB1*0901 (P=2.55x10(-5)) were the subtypes most susceptible to SSc in Korean subjects. In US Caucasians, 2 pairs of SNPs, rs7763822/rs7764491 and rs3117230/rs3128965, showed strong association with SSc patients who had either circulating anti-DNA topoisomerase I (P=7.58x10(-17)/4.84x10(-16)) or anticentromere autoantibodies (P=1.12x10(-3)/3.2x10(-5)), respectively.RESULTSThe single-nucleotide polymorphisms (SNPs) (rs3128930, rs7763822, rs7764491, rs3117230, and rs3128965) of HLA-DPB1 and DPB2 on chromosome 6 formed a distinctive peak with log P values for association with SSc susceptibility (P=8.16x10(-13)). Subtyping analysis of HLA-DPB1 showed that DPB1*1301 (P=7.61x10(-8)) and DPB1*0901 (P=2.55x10(-5)) were the subtypes most susceptible to SSc in Korean subjects. In US Caucasians, 2 pairs of SNPs, rs7763822/rs7764491 and rs3117230/rs3128965, showed strong association with SSc patients who had either circulating anti-DNA topoisomerase I (P=7.58x10(-17)/4.84x10(-16)) or anticentromere autoantibodies (P=1.12x10(-3)/3.2x10(-5)), respectively.The results of our genome-wide association study in Korean subjects indicate that the region of HLA-DPB1 and DPB2 contains the loci most susceptible to SSc in a Korean population. The confirmatory studies in US Caucasians indicate that specific SNPs of HLA-DPB1 and/or DPB2 are strongly associated with US Caucasian patients with SSc who are positive for anti-DNA topoisomerase I or anticentromere autoantibodies.CONCLUSIONThe results of our genome-wide association study in Korean subjects indicate that the region of HLA-DPB1 and DPB2 contains the loci most susceptible to SSc in a Korean population. The confirmatory studies in US Caucasians indicate that specific SNPs of HLA-DPB1 and/or DPB2 are strongly associated with US Caucasian patients with SSc who are positive for anti-DNA topoisomerase I or anticentromere autoantibodies. Objective To identify systemic sclerosis (SSc) susceptibility loci via a genome‐wide association study. Methods A genome‐wide association study was performed in 137 patients with SSc and 564 controls from Korea using the Affymetrix Human SNP Array 5.0. After fine‐mapping studies, the results were replicated in 1,107 SSc patients and 2,747 controls from a US Caucasian population. Results The single‐nucleotide polymorphisms (SNPs) (rs3128930, rs7763822, rs7764491, rs3117230, and rs3128965) of HLA–DPB1 and DPB2 on chromosome 6 formed a distinctive peak with log P values for association with SSc susceptibility (P = 8.16 × 10−13). Subtyping analysis of HLA–DPB1 showed that DPB1*1301 (P = 7.61 × 10−8) and DPB1*0901 (P = 2.55 × 10−5) were the subtypes most susceptible to SSc in Korean subjects. In US Caucasians, 2 pairs of SNPs, rs7763822/rs7764491 and rs3117230/rs3128965, showed strong association with SSc patients who had either circulating anti–DNA topoisomerase I (P = 7.58 × 10−17/4.84 × 10−16) or anticentromere autoantibodies (P = 1.12 × 10−3/3.2 × 10−5), respectively. Conclusion The results of our genome‐wide association study in Korean subjects indicate that the region of HLA–DPB1 and DPB2 contains the loci most susceptible to SSc in a Korean population. The confirmatory studies in US Caucasians indicate that specific SNPs of HLA–DPB1 and/or DPB2 are strongly associated with US Caucasian patients with SSc who are positive for anti–DNA topoisomerase I or anticentromere autoantibodies. Objective To identify systemic sclerosis (SSc) susceptibility loci via a genome-wide association study. Methods A genome-wide association study was performed in 137 patients with SSc and 564 controls from Korea using the Affymetrix Human SNP Array 5.0. After fine-mapping studies, the results were replicated in 1,107 SSc patients and 2,747 controls from a US Caucasian population. Results The single-nucleotide polymorphisms (SNPs) (rs3128930, rs7763822, rs7764491, rs3117230, and rs3128965) of HLA-DPB1 and DPB2 on chromosome 6 formed a distinctive peak with log P values for association with SSc susceptibility (P = 8.16 X 10-13). Subtyping analysis of HLA-DPB1 showed that DPB1*1301 (P = 7.61 X 10-8) and DPB1*0901 (P = 2.55 X 10-5) were the subtypes most susceptible to SSc in Korean subjects. In US Caucasians, 2 pairs of SNPs, rs7763822/rs7764491 and rs3117230/rs3128965, showed strong association with SSc patients who had either circulating anti-DNA topoisomerase I (P = 7.58 X 10-17/4.84 X 10-16) or anticentromere autoantibodies (P = 1.12 X 10-3/3.2 X 10-5), respectively. Conclusion The results of our genome-wide association study in Korean subjects indicate that the region of HLA-DPB1 and DPB2 contains the loci most susceptible to SSc in a Korean population. The confirmatory studies in US Caucasians indicate that specific SNPs of HLA-DPB1 and/or DPB2 are strongly associated with US Caucasian patients with SSc who are positive for anti-DNA topoisomerase I or anticentromere autoantibodies. |
| Author | Xiong, Momiao Lee, Jong Eun Reveille, John D. Park, Min Young Song, Ran Mayes, Maureen D. Lee, Eun Young Lee, Yun Jong Lee, Eun Bong Shin, Eun Soon Kim, Jin Hyun Choi, Ji Yong Park, Ji Ah Song, Yeong Wook Yoo, Yeon Kyeong Arnett, Frank C. Zhou, Xiaodong |
| AuthorAffiliation | 2 DNA Link Inc, Seoul, Korea 1 Division of Rheumatology and Clinical Immunogenetics, Department of Internal Medicine, University of Texas Medical School at Houston, Houston TX. USA 3 Department of Biostatistics, University of Texas School of Public Health 5 Medical Research Center, Seoul National University, Seoul Korea 4 Department of Internal Medicine, Department of Immunology, Seoul National University College of Medicine, Seoul, Korea |
| AuthorAffiliation_xml | – name: 2 DNA Link Inc, Seoul, Korea – name: 1 Division of Rheumatology and Clinical Immunogenetics, Department of Internal Medicine, University of Texas Medical School at Houston, Houston TX. USA – name: 3 Department of Biostatistics, University of Texas School of Public Health – name: 4 Department of Internal Medicine, Department of Immunology, Seoul National University College of Medicine, Seoul, Korea – name: 5 Medical Research Center, Seoul National University, Seoul Korea |
| Author_xml | – sequence: 1 givenname: Xiaodong surname: Zhou fullname: Zhou, Xiaodong – sequence: 2 givenname: Jong Eun surname: Lee fullname: Lee, Jong Eun – sequence: 3 givenname: Frank C. surname: Arnett fullname: Arnett, Frank C. – sequence: 4 givenname: Momiao surname: Xiong fullname: Xiong, Momiao – sequence: 5 givenname: Min Young surname: Park fullname: Park, Min Young – sequence: 6 givenname: Yeon Kyeong surname: Yoo fullname: Yoo, Yeon Kyeong – sequence: 7 givenname: Eun Soon surname: Shin fullname: Shin, Eun Soon – sequence: 8 givenname: John D. surname: Reveille fullname: Reveille, John D. – sequence: 9 givenname: Maureen D. surname: Mayes fullname: Mayes, Maureen D. – sequence: 10 givenname: Jin Hyun surname: Kim fullname: Kim, Jin Hyun – sequence: 11 givenname: Ran surname: Song fullname: Song, Ran – sequence: 12 givenname: Ji Yong surname: Choi fullname: Choi, Ji Yong – sequence: 13 givenname: Ji Ah surname: Park fullname: Park, Ji Ah – sequence: 14 givenname: Yun Jong surname: Lee fullname: Lee, Yun Jong – sequence: 15 givenname: Eun Young surname: Lee fullname: Lee, Eun Young – sequence: 16 givenname: Yeong Wook surname: Song fullname: Song, Yeong Wook – sequence: 17 givenname: Eun Bong surname: Lee fullname: Lee, Eun Bong email: leb7616@snu.ac.kr |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/19950302$$D View this record in MEDLINE/PubMed |
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| Notes | Drs. Zhou and Jong Eun Lee contributed equally to this work. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Both authors equally contributed to the study. |
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| Snippet | Objective
To identify systemic sclerosis (SSc) susceptibility loci via a genome‐wide association study.
Methods
A genome‐wide association study was performed... To identify systemic sclerosis (SSc) susceptibility loci via a genome-wide association study. A genome-wide association study was performed in 137 patients... To identify systemic sclerosis (SSc) susceptibility loci via a genome-wide association study.OBJECTIVETo identify systemic sclerosis (SSc) susceptibility loci... Objective To identify systemic sclerosis (SSc) susceptibility loci via a genome-wide association study. Methods A genome-wide association study was performed... |
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| SubjectTerms | Adolescent Adult Aged Autoantibodies - blood Child Child, Preschool DNA - genetics DNA - isolation & purification DNA Polymerase II - genetics DNA Topoisomerases, Type I - immunology Female Genetic Loci Genetic Predisposition to Disease Genome-Wide Association Study HLA-DP Antigens - genetics HLA-DP beta-Chains Humans Korea - epidemiology Male Middle Aged North America - epidemiology Polymorphism, Single Nucleotide Scleroderma, Systemic - ethnology Scleroderma, Systemic - genetics Scleroderma, Systemic - immunology Young Adult |
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| Title | HLA–DPB1 and DPB2 are genetic loci for systemic sclerosis: A genome‐wide association study in Koreans with replication in North Americans |
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