Evidence map›Paper›PMID 26814708›Full record

ArticleArthritis & rheumatology (Hoboken, N.J.)2016

Effects of Complement C4 Gene Copy Number Variations, Size Dichotomy, and C4A Deficiency on Genetic Risk and Clinical Presentation of Systemic Lupus Erythematosus in East Asian Populations.

Ji Yih Chen, Yee Ling Wu, Mo Yin Mok, Yeong-Jian Jan Wu, Katherine E Lintner, Chin-Man Wang, Erwin K Chung, Yan Yang, Bi Zhou, Huanyu Wang and 8 more

Abstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Arthritis & rheumatology (Hoboken, N.J.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 1 pooled it
8.1field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

39 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.

  1. Pooled it
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  3. Review
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  5. Article
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  7. Review
  8. Review
  9. Review
  10. Low copy numbers of complementAnnals of the rheumatic diseases · 2023
    Article
  11. Article
  12. Article
  13. Review
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  15. Article
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  18. Article
  19. Contributions of de novo variants to systemic lupus erythematosus.European journal of human genetics : EJHG · 2021
    Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 6 institutions in 4 countries.

Ji Yih Chen *Department of Medicine, Division of Allergy, Immunology and Rheumatology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan, Republic of China.
Yee Ling Wu *Center for Molecular and Human Genetics, The Research Institute and Division of Pediatric Rheumatology, Nationwide Children's Hospital; and Department of Pediatrics, The Ohio State University, 700 Children's Drive, Columbus, Ohio 43205, USA.
Mo Yin MokDivision of Rheumatology, Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Yeong-Jian Jan WuDepartment of Medicine, Division of Allergy, Immunology and Rheumatology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan, Republic of China.
Katherine E LintnerCenter for Molecular and Human Genetics, The Research Institute and Division of Pediatric Rheumatology, Nationwide Children's Hospital; and Department of Pediatrics, The Ohio State University, 700 Children's Drive, Columbus, Ohio 43205, USA.
Chin-Man WangDepartment of Rehabilitation, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan, Republic of China.
Erwin K ChungCenter for Molecular and Human Genetics, The Research Institute and Division of Pediatric Rheumatology, Nationwide Children's Hospital; and Department of Pediatrics, The Ohio State University, 700 Children's Drive, Columbus, Ohio 43205, USA.
Yan YangCenter for Molecular and Human Genetics, The Research Institute and Division of Pediatric Rheumatology, Nationwide Children's Hospital; and Department of Pediatrics, The Ohio State University, 700 Children's Drive, Columbus, Ohio 43205, USA.
Bi ZhouCenter for Molecular and Human Genetics, The Research Institute and Division of Pediatric Rheumatology, Nationwide Children's Hospital; and Department of Pediatrics, The Ohio State University, 700 Children's Drive, Columbus, Ohio 43205, USA.
Huanyu WangCenter for Molecular and Human Genetics, The Research Institute and Division of Pediatric Rheumatology, Nationwide Children's Hospital; and Department of Pediatrics, The Ohio State University, 700 Children's Drive, Columbus, Ohio 43205, USA.
Dennis YuCenter for Molecular and Human Genetics, The Research Institute and Division of Pediatric Rheumatology, Nationwide Children's Hospital; and Department of Pediatrics, The Ohio State University, 700 Children's Drive, Columbus, Ohio 43205, USA.
Alaaedin AlhomoshCenter for Molecular and Human Genetics, The Research Institute and Division of Pediatric Rheumatology, Nationwide Children's Hospital; and Department of Pediatrics, The Ohio State University, 700 Children's Drive, Columbus, Ohio 43205, USA.
Karla JonesCenter for Molecular and Human Genetics, The Research Institute and Division of Pediatric Rheumatology, Nationwide Children's Hospital; and Department of Pediatrics, The Ohio State University, 700 Children's Drive, Columbus, Ohio 43205, USA.
Charles H SpencerCenter for Molecular and Human Genetics, The Research Institute and Division of Pediatric Rheumatology, Nationwide Children's Hospital; and Department of Pediatrics, The Ohio State University, 700 Children's Drive, Columbus, Ohio 43205, USA.
Haikady N NagarajaDivision of Biostatistics, College of Public Health, The Ohio State University, Columbus, Ohio 43201, USA.
Yu Lung LauDepartment of Pediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Chak-Sing LauDivision of Rheumatology, Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
C Yung YuCenter for Molecular and Human Genetics, The Research Institute and Division of Pediatric Rheumatology, Nationwide Children's Hospital; and Department of Pediatrics, The Ohio State University, 700 Children's Drive, Columbus, Ohio 43205, USA.
The Ohio State University · USNationwide Children's Hospital · USChang Gung Memorial Hospital · TWUniversity of Hong Kong · HKChang Gung University · TWChinese University of Hong Kong · CN

Funding

Variations of Complement in Immunity and DiseasesR01AR050078 · NIAMS · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI YU, CHACK Y · 2003 to 2007
$1.6M
Complement Genetics and Clinical Variability of Systemic Lupus ErythematosusR01AR054459 · NIAMS · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI YU, CHACK Y · 2008 to 2012
$1.5M
NIAMS NIH HHS R01 AR050078NIAMS NIH HHS R01 AR054459
6 · The paper itself

Abstract

objectiveHuman complement C4 is complex, with multiple layers of diversity. The aims of this study were to elucidate the copy number variations (CNVs) of C4A and C4B in relation to disease risk in systemic lupus erythematosus (SLE), and to compare the basis of race-specific C4A deficiency between East Asians and individuals of European descent.

methodsThe East Asian study population included 999 SLE patients and 1,347 healthy subjects. Variations in gene copy numbers (GCNs) of total C4, C4A, and C4B, as well as C4-Long and C4-Short genes, were determined and validated using independent genotyping technologies. Genomic regions with C4B96 were investigated to determine the basis of the most basic C4B protein occurring concurrently with C4A deficiency.

resultsIn East Asians, high GCNs of total C4 and C4A were strongly protective against SLE, whereas low and medium GCNs of total C4 and C4A, and the absence of C4-Short genes, were risk factors for SLE. Homozygous C4A deficiency was infrequent in East Asian subjects, but had an odds ratio (OR) of 12.4 (P = 0.0015) for SLE disease susceptibility. Low serum complement levels were strongly associated with low GCNs of total C4 (OR 3.19, P = 7.3 × 10(-7) ) and C4B (OR 2.53, P = 2.5 × 10(-5) ). Patients with low serum complement levels had high frequencies of anti-double-stranded DNA antibodies (OR 4.96, P = 9.7 × 10(-17) ), hemolytic anemia (OR 3.89, P = 3.6 × 10(-10) ), and renal disease (OR 2.18, P = 8.5 × 10(-6) ). The monomodular-Short haplotype found to be prevalent in European Americans with C4A deficiency, which was in linkage disequilibrium with HLA-DRB1*0301, was scarce in East Asians. Instead, most East Asian subjects with C4A deficiency were found to have a recombinant haplotype with bimodular C4-Long and C4-Short genes, encoding C4B1 and C4B96, which was linked to HLA-DRB1*1501. DNA sequencing revealed an E920K polymorphism in C4B96.

conclusionC4 CNVs and deficiency of C4A both play an important role in the risk and manifestations of SLE in East Asian and European populations.

Indexed as

DNA Copy Number VariationsAdultAsian PeopleComplement C4aComplement C4bFemaleHereditary Complement Deficiency DiseasesHumansImmunologic Deficiency SyndromesLupus Erythematosus, SystemicMaleRisk AssessmentRisk FactorsWhite PeopleComplement C4aComplement C4b

Identifiers

PMID26814708
PMCPMC5114127
OpenAlexW2411862915

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.