PMID- 25927497
OWN - NLM
STAT- MEDLINE
DCOM- 20160119
LR  - 20221207
IS  - 1478-6362 (Electronic)
IS  - 1478-6354 (Print)
IS  - 1478-6354 (Linking)
VI  - 17
IP  - 1
DP  - 2015 Apr 18
TI  - Anti-citrullinated peptide/protein antibody (ACPA)-negative RA shares a large 
      proportion of susceptibility loci with ACPA-positive RA: a meta-analysis of 
      genome-wide association study in a Japanese population.
PG  - 104
LID - 10.1186/s13075-015-0623-4 [doi]
LID - 104
AB  - INTRODUCTION: Although susceptibility genes for anti-citrullinated 
      peptide/protein antibodies (ACPA)-positive rheumatoid arthritis (RA) have been 
      successfully discovered by genome-wide association studies (GWAS), little is 
      known about the genetic background of ACPA-negative RA. We intended to elucidate 
      genetic background of ACPA-negative RA. METHOD: We performed a meta-analysis of 
      GWAS comprising 670 ACPA-negative RA and 16,891 controls for 1,948,138 markers, 
      followed by a replication study of the top 35 single nucleotide polymorphisms 
      (SNPs) using 916 cases and 3,764 controls. Inverse-variance method was applied to 
      assess overall effects. To assess overlap of susceptibility loci between 
      ACPA-positive and -negative RA, odds ratios (ORs) of the 21 susceptibility 
      markers to RA in Japanese were compared between the two subsets. In addition, 
      SNPs were stratified by the p-values in GWAS meta-analysis for either 
      ACPA-positive RA or ACPA-negative RA to address the question whether 
      weakly-associated genes were also shared. The correlations between ACPA-positive 
      RA and the subpopulations of ACPA-negative RA (rheumatoid factor (RF)-positive 
      and RF-negative subsets) were also addressed. RESULTS: Rs6904716 in LEMD2 of the 
      human leukocyte antigen (HLA) locus showed a borderline association with 
      ACPA-negative RA (overall p = 5.7 x 10(-8)), followed by rs6986423 in CSMD1 
      (p = 2.4 x 10(-6)) and rs17727339 in FCRL3 (p = 1.4 x 10(-5)). ACPA-negative RA 
      showed significant correlations of ORs with ACPA-positive RA for the 21 
      susceptibility SNPs and non-HLA SNPs with p-values far from significance. These 
      significant correlations with ACPA-positive RA were true for ACPA-negative 
      RF-positive and ACPA-negative RF-negative RA. On the contrary, positive 
      correlations were not observed between the ACPA-negative two subpopulations. 
      CONCLUSION: Many of the susceptibility loci were shared between ACPA-positive and 
      -negative RA.
FAU - Terao, Chikashi
AU  - Terao C
AD  - Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, 
      Japan. a0001101@kuhp.kyoto-u.ac.jp.
FAU - Ohmura, Koichiro
AU  - Ohmura K
AD  - Department of Rheumatology and Clinical Immunology, Kyoto University Graduate 
      School of Medicine, Kyoto, 606-8507, Japan. ohmurako@kuhp.kyoto-u.ac.jp.
FAU - Kochi, Yuta
AU  - Kochi Y
AD  - Laboratory for Autoimmune Diseases, Center for Genomic Medicine, RIKEN, Yokohama, 
      Japan. ykochi@src.riken.jp.
FAU - Ikari, Katsunori
AU  - Ikari K
AD  - Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan. 
      kikari@mac.com.
FAU - Okada, Yukinori
AU  - Okada Y
AD  - Department of Human Genetics and Disease Diversity, Graduate School of Medical 
      and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan. 
      yokada.brc@tmd.ac.jp.
FAU - Shimizu, Masakazu
AU  - Shimizu M
AD  - Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, 
      Japan. shimmy@kuhp.kyoto-u.ac.jp.
FAU - Nishina, Naoshi
AU  - Nishina N
AD  - Division of Rheumatology, Department of Internal Medicine, Keio University School 
      of Medicine, Tokyo, Japan. nnnmd11@hotmail.com.
FAU - Suzuki, Akari
AU  - Suzuki A
AD  - Laboratory for Autoimmune Diseases, Center for Genomic Medicine, RIKEN, Yokohama, 
      Japan. akaris@src.riken.jp.
FAU - Myouzen, Keiko
AU  - Myouzen K
AD  - Laboratory for Autoimmune Diseases, Center for Genomic Medicine, RIKEN, Yokohama, 
      Japan. keimyouzen@src.riken.jp.
FAU - Kawaguchi, Takahisa
AU  - Kawaguchi T
AD  - Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, 
      Japan. tkawa@genome.med.kyoto-u.ac.jp.
FAU - Takahashi, Meiko
AU  - Takahashi M
AD  - Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, 
      Japan. meiko@genome.med.kyoto-u.ac.jp.
FAU - Takasugi, Kiyoshi
AU  - Takasugi K
AD  - Dohgo Spa Hospital, Matsuyama, Japan. keetakas@ehime.med.or.jp.
FAU - Murasawa, Akira
AU  - Murasawa A
AD  - Department of Rheumatology, Niigata Rheumatic Center, Niigata, Japan. 
      med@ra-center.com.
FAU - Mizuki, Shinichi
AU  - Mizuki S
AD  - The Centre for Rheumatic Diseases, Matsuyama Red Cross Hospital, Matsuyama, 
      Japan. smizuki@matsuyama.jrc.or.jp.
FAU - Iwahashi, Mitsuhiro
AU  - Iwahashi M
AD  - Higashihiroshima Memorial Hospital, Hiroshima, Japan. ajisu@hotmail.com.
FAU - Funahashi, Keiko
AU  - Funahashi K
AD  - Pharm C, Matsubara Mayflower Hospital, 944-25 Fujita, Kato City, Hyogo, Japan. 
      kansetsusaisei123@cup.ocn.ne.jp.
FAU - Natsumeda, Masamitsu
AU  - Natsumeda M
AD  - Kurashiki Sweet Hospital, Kurashiki, Japan. zaraspook3hook@yahoo.co.jp.
FAU - Furu, Moritoshi
AU  - Furu M
AD  - Department of the Control for Rheumatic Diseases, Kyoto University Graduate 
      School of Medicine, Kyoto, Japan. morifuru@kuhp.kyoto-u.ac.jp.
FAU - Hashimoto, Motomu
AU  - Hashimoto M
AD  - Department of the Control for Rheumatic Diseases, Kyoto University Graduate 
      School of Medicine, Kyoto, Japan. mohashim@kuhp.kyoto-u.ac.jp.
FAU - Ito, Hiromu
AU  - Ito H
AD  - Department of the Control for Rheumatic Diseases, Kyoto University Graduate 
      School of Medicine, Kyoto, Japan. hiromu@kuhp.kyoto-u.ac.jp.
FAU - Fujii, Takao
AU  - Fujii T
AD  - Department of the Control for Rheumatic Diseases, Kyoto University Graduate 
      School of Medicine, Kyoto, Japan. takfujii@kuhp.kyoto-u.ac.jp.
FAU - Ezawa, Kazuhiko
AU  - Ezawa K
AD  - Kurashiki Sweet Hospital, Kurashiki, Japan. ky-6182@rice.ocn.ne.jp.
FAU - Matsubara, Tsukasa
AU  - Matsubara T
AD  - Matsubara Mayflower Hospital, 944-25 Fujita, Kato City, Hyogo, Japan. 
      mats@mayflower-hp.jp.
FAU - Takeuchi, Tsutomu
AU  - Takeuchi T
AD  - Division of Rheumatology, Department of Internal Medicine, Keio University School 
      of Medicine, Tokyo, Japan. tsutake@z5.keio.jp.
FAU - Kubo, Michiaki
AU  - Kubo M
AD  - Laboratory for Autoimmune Diseases, Center for Genomic Medicine, RIKEN, Yokohama, 
      Japan. mkubo@src.riken.jp.
FAU - Yamada, Ryo
AU  - Yamada R
AD  - Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, 
      Japan. ryamada@genome.med.kyoto-u.ac.jp.
FAU - Taniguchi, Atsuo
AU  - Taniguchi A
AD  - Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan. 
      amtanigu@ior.twmu.ac.jp.
FAU - Yamanaka, Hisashi
AU  - Yamanaka H
AD  - Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan. 
      yamanaka@ior.twmu.ac.jp.
FAU - Momohara, Shigeki
AU  - Momohara S
AD  - Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan. 
      smomohara@ior.twmu.ac.jp.
FAU - Yamamoto, Kazuhiko
AU  - Yamamoto K
AD  - Laboratory for Autoimmune Diseases, Center for Genomic Medicine, RIKEN, Yokohama, 
      Japan. yamamoto-tky@umin.ac.jp.
FAU - Mimori, Tsuneyo
AU  - Mimori T
AD  - Department of Rheumatology and Clinical Immunology, Kyoto University Graduate 
      School of Medicine, Kyoto, 606-8507, Japan. mimorit@kuhp.kyoto-u.ac.jp.
FAU - Matsuda, Fumihiko
AU  - Matsuda F
AD  - Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, 
      Japan. fumi@genome.med.kyoto-u.ac.jp.
AD  - Institut National de la Sante et de la Recherche Medicale (INSERM) Unite U852, 
      Kyoto University Graduate School of Medicine, Kyoto, Japan. 
      fumi@genome.med.kyoto-u.ac.jp.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20150418
PL  - England
TA  - Arthritis Res Ther
JT  - Arthritis research & therapy
JID - 101154438
RN  - 0 (Peptides, Cyclic)
RN  - 0 (cyclic citrullinated peptide)
SB  - IM
MH  - Arthritis, Rheumatoid/ethnology/*genetics/immunology
MH  - Asian People/*genetics
MH  - Female
MH  - Genetic Loci
MH  - Genetic Predisposition to Disease/*epidemiology
MH  - *Genome-Wide Association Study
MH  - Genotype
MH  - Humans
MH  - Japan
MH  - Male
MH  - Peptides, Cyclic/*genetics/immunology
MH  - Polymorphism, Single Nucleotide
MH  - Reference Values
PMC - PMC4431175
EDAT- 2015/05/01 06:00
MHDA- 2016/01/20 06:00
PMCR- 2015/04/18
CRDT- 2015/05/01 06:00
PHST- 2014/07/28 00:00 [received]
PHST- 2015/04/08 00:00 [accepted]
PHST- 2015/05/01 06:00 [entrez]
PHST- 2015/05/01 06:00 [pubmed]
PHST- 2016/01/20 06:00 [medline]
PHST- 2015/04/18 00:00 [pmc-release]
AID - 10.1186/s13075-015-0623-4 [pii]
AID - 623 [pii]
AID - 10.1186/s13075-015-0623-4 [doi]
PST - epublish
SO  - Arthritis Res Ther. 2015 Apr 18;17(1):104. doi: 10.1186/s13075-015-0623-4.