#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#
preLekára.sk / Odborné časopisy / PLOS Genetics / 2011 - 3

Differential Genetic Associations for Systemic Lupus Erythematosus Based on Anti–dsDNA Autoantibody Production

English version České info

Systemic lupus erythematosus (SLE) is a clinically heterogeneous, systemic autoimmune disease characterized by autoantibody formation. Previously published genome-wide association studies (GWAS) have investigated SLE as a single phenotype. Therefore, we conducted a GWAS to identify genetic factors associated with anti–dsDNA autoantibody production, a SLE–related autoantibody with diagnostic and clinical importance. Using two independent datasets, over 400,000 single nucleotide polymorphisms (SNPs) were studied in a total of 1,717 SLE cases and 4,813 healthy controls. Anti–dsDNA autoantibody positive (anti–dsDNA +, n = 811) and anti–dsDNA autoantibody negative (anti–dsDNA –, n = 906) SLE cases were compared to healthy controls and to each other to identify SNPs associated specifically with these SLE subtypes. SNPs in the previously identified SLE susceptibility loci STAT4, IRF5, ITGAM, and the major histocompatibility complex were strongly associated with anti–dsDNA + SLE. Far fewer and weaker associations were observed for anti–dsDNA –⁠ SLE. For example, rs7574865 in STAT4 had an OR for anti–dsDNA + SLE of 1.77 (95% CI 1.57–1.99, p = 2.0E-20) compared to an OR for anti–dsDNA –⁠ SLE of 1.26 (95% CI 1.12–1.41, p = 2.4E-04), with pheterogeneity<0.0005. SNPs in the SLE susceptibility loci BANK1, KIAA1542, and UBE2L3 showed evidence of association with anti–dsDNA + SLE and were not associated with anti–dsDNA –⁠ SLE. In conclusion, we identified differential genetic associations with SLE based on anti–dsDNA autoantibody production. Many previously identified SLE susceptibility loci may confer disease risk through their role in autoantibody production and be more accurately described as autoantibody propensity loci. Lack of strong SNP associations may suggest that other types of genetic variation or non-genetic factors such as environmental exposures have a greater impact on susceptibility to anti–dsDNA –⁠ SLE.

Vyšlo v časopise: Differential Genetic Associations for Systemic Lupus Erythematosus Based on Anti–dsDNA Autoantibody Production. PLoS Genet 7(3): e32767. doi:10.1371/journal.pgen.1001323
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1001323

Souhrn

Systemic lupus erythematosus (SLE) is a clinically heterogeneous, systemic autoimmune disease characterized by autoantibody formation. Previously published genome-wide association studies (GWAS) have investigated SLE as a single phenotype. Therefore, we conducted a GWAS to identify genetic factors associated with anti–dsDNA autoantibody production, a SLE–related autoantibody with diagnostic and clinical importance. Using two independent datasets, over 400,000 single nucleotide polymorphisms (SNPs) were studied in a total of 1,717 SLE cases and 4,813 healthy controls. Anti–dsDNA autoantibody positive (anti–dsDNA +, n = 811) and anti–dsDNA autoantibody negative (anti–dsDNA –, n = 906) SLE cases were compared to healthy controls and to each other to identify SNPs associated specifically with these SLE subtypes. SNPs in the previously identified SLE susceptibility loci STAT4, IRF5, ITGAM, and the major histocompatibility complex were strongly associated with anti–dsDNA + SLE. Far fewer and weaker associations were observed for anti–dsDNA –⁠ SLE. For example, rs7574865 in STAT4 had an OR for anti–dsDNA + SLE of 1.77 (95% CI 1.57–1.99, p = 2.0E-20) compared to an OR for anti–dsDNA –⁠ SLE of 1.26 (95% CI 1.12–1.41, p = 2.4E-04), with pheterogeneity<0.0005. SNPs in the SLE susceptibility loci BANK1, KIAA1542, and UBE2L3 showed evidence of association with anti–dsDNA + SLE and were not associated with anti–dsDNA –⁠ SLE. In conclusion, we identified differential genetic associations with SLE based on anti–dsDNA autoantibody production. Many previously identified SLE susceptibility loci may confer disease risk through their role in autoantibody production and be more accurately described as autoantibody propensity loci. Lack of strong SNP associations may suggest that other types of genetic variation or non-genetic factors such as environmental exposures have a greater impact on susceptibility to anti–dsDNA –⁠ SLE.

Zdroje

1. PisetskyD

2001 Systemic Lupus Erythematosus: Epidemiology, Pathology, and Pathogenesis.

KlippelJ

Primer of the Rheumatic Diseases. 12 ed  Atlanta Arthritis Foundation

2. ArbuckleMR

McClainMT

RubertoneMV

ScofieldRH

DennisGJ

2003 Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med 349 1526 1533

3. BuyonJ

2008 Systemic Lupus Erythematosus: A. Clinical and Laboratory Features.

KlippelJ

Primer on the Rheumatic Diseases. 13 ed  New York, NY  Springer 303 318

4. IsenbergDA

MansonJJ

EhrensteinMR

RahmanA

2007 Fifty years of anti-ds DNA antibodies: are we approaching journey's end? Rheumatology (Oxford) 46 1052 1056

5. TanEM

CohenAS

FriesJF

MasiAT

McShaneDJ

1982 The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25 1271 1277

6. HochbergMC

1997 Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40 1725

7. GatevaV

SandlingJK

HomG

TaylorKE

ChungSA

2009 A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus. Nat Genet 41 1228 1233

8. HomG

GrahamRR

ModrekB

TaylorKE

OrtmannW

2008 Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX. N Engl J Med 358 900 909

9. HarleyJB

Alarcon-RiquelmeME

CriswellLA

JacobCO

KimberlyRP

2008 Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci. Nat Genet 40 204 210

10. HunterDJ

KraftP

JacobsKB

CoxDG

YeagerM

2007 A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer. Nat Genet 39 870 874

11. AlarconGS

McGwinGJr

PetriM

ReveilleJD

Ramsey-GoldmanR

2002 Baseline characteristics of a multiethnic lupus cohort: PROFILE. Lupus 11 95 101

12. PurcellS

NealeB

Todd-BrownK

ThomasL

FerreiraMA

2007 PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81 559 575

13. RemmersEF

PlengeRM

LeeAT

GrahamRR

HomG

2007 STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus. N Engl J Med 357 977 986

14. GrahamRR

KozyrevSV

BaechlerEC

ReddyMV

PlengeRM

2006 A common haplotype of interferon regulatory factor 5 (IRF5) regulates splicing and expression and is associated with increased risk of systemic lupus erythematosus. Nat Genet 38 550 555

15. SigurdssonS

NordmarkG

GarnierS

GrundbergE

KwanT

2008 A risk haplotype of STAT4 for systemic lupus erythematosus is over-expressed, correlates with anti–dsDNA and shows additive effects with two risk alleles of IRF5. Hum Mol Genet 17 2868 2876

16. TaylorKE

RemmersEF

LeeAT

OrtmannWA

PlengeRM

2008 Specificity of the STAT4 genetic association for severe disease manifestations of systemic lupus erythematosus. PLoS Genet 4 e1000084 doi:10.1371/journal.pgen.1000084

17. BurgnerD

DavilaS

BreunisWB

NgSB

LiY

2009 A genome-wide association study identifies novel and functionally related susceptibility Loci for Kawasaki disease. PLoS Genet 5 e1000319 doi:10.1371/journal.pgen.1000319

18. FernandoMM

StevensCR

WalshEC

De JagerPL

GoyetteP

2008 Defining the role of the MHC in autoimmunity: a review and pooled analysis. PLoS Genet 4 e1000024 doi:10.1371/journal.pgen.1000024

19. BarcellosLF

MaySL

RamsayPP

QuachHL

LaneJA

2009 High-density SNP screening of the major histocompatibility complex in systemic lupus erythematosus demonstrates strong evidence for independent susceptibility regions. PLoS Genet 5 e1000696 doi:10.1371/journal.pgen.1000696

20. TaylorKE

ChungSA

GrahamRR

OrtmannWA

LeeAT

2011 Risk alleles for systemic lupus erythematosus in a large case-control collection and associations with clinical subphenotypes. PLoS Genet 7 e1001311 doi:10.1371/journal.pgen.1001311

21. van der Helm-van MilAH

VerpoortKN

BreedveldFC

HuizingaTW

ToesRE

2006 The HLA-DRB1 shared epitope alleles are primarily a risk factor for anti-cyclic citrullinated peptide antibodies and are not an independent risk factor for development of rheumatoid arthritis. Arthritis Rheum 54 1117 1121

22. MorganAW

RobinsonJI

ConaghanPG

MartinSG

HensorEM

2010 Evaluation of the rheumatoid arthritis susceptibility loci HLA-DRB1, PTPN22, OLIG3/TNFAIP3, STAT4 and TRAF1/C5 in an inception cohort. Arthritis Res Ther 12 R57

23. LeeHS

RemmersEF

LeJM

KastnerDL

BaeSC

2007 Association of STAT4 with rheumatoid arthritis in the Korean population. Mol Med 13 455 460

24. CooperGS

GilbertKM

GreidingerEL

JamesJA

PfauJC

2008 Recent advances and opportunities in research on lupus: environmental influences and mechanisms of disease. Environ Health Perspect 116 695 702

25. Sarzi-PuttiniP

AtzeniF

IaccarinoL

DoriaA

2005 Environment and systemic lupus erythematosus: an overview. Autoimmunity 38 465 472

26. McCartyDJ

ManziS

MedsgerTAJr

Ramsey-GoldmanR

LaPorteRE

1995 Incidence of systemic lupus erythematosus. Race and gender differences. Arthritis Rheum 38 1260 1270

27. JohnsonAE

GordonC

PalmerRG

BaconPA

1995 The prevalence and incidence of systemic lupus erythematosus in Birmingham, England. Relationship to ethnicity and country of birth. Arthritis Rheum 38 551 558

28. MarchiniJ

HowieB

MyersS

McVeanG

DonnellyP

2007 A new multipoint method for genome-wide association studies by imputation of genotypes. Nat Genet 39 906 913

29. PriceAL

PattersonNJ

PlengeRM

WeinblattME

ShadickNA

2006 Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 38 904 909

Štítky
Genetika Reprodukčná medicína
Článek Whole-Exome Re-Sequencing in a Family Quartet Identifies Mutations As the Cause of a Novel Skeletal Dysplasia
Článek Origin-Dependent Inverted-Repeat Amplification: A Replication-Based Model for Generating Palindromic Amplicons
Článek Testing for an Unusual Distribution of Rare Variants
Článek Limited dCTP Availability Accounts for Mitochondrial DNA Depletion in Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE)
Článek FUS Transgenic Rats Develop the Phenotypes of Amyotrophic Lateral Sclerosis and Frontotemporal Lobar Degeneration
Článek Repeat Associated Non-ATG Translation Initiation: One DNA, Two Transcripts, Seven Reading Frames, Potentially Nine Toxic Entities!
Článek Initial Mutations Direct Alternative Pathways of Protein Evolution
Článek Dopamine Signalling in Mushroom Bodies Regulates Temperature-Preference Behaviour in
Článek Sensing of Replication Stress and Mec1 Activation Act through Two Independent Pathways Involving the 9-1-1 Complex and DNA Polymerase ε
Článek Genetic Regulation by NLA and MicroRNA827 for Maintaining Nitrate-Dependent Phosphate Homeostasis in
Článek Identification of a Novel Type of Spacer Element Required for Imprinting in Fission Yeast
Článek Chiasmata Promote Monopolar Attachment of Sister Chromatids and Their Co-Segregation toward the Proper Pole during Meiosis I
Článek Global Analysis of the Relationship between JIL-1 Kinase and Transcription
Článek H3K9me2/3 Binding of the MBT Domain Protein LIN-61 Is Essential for Vulva Development
Článek REVEILLE8 and PSEUDO-REPONSE REGULATOR5 Form a Negative Feedback Loop within the Arabidopsis Circadian Clock
Článek A Novel Unstable Duplication Upstream of Predisposes to a Breed-Defining Skin Phenotype and a Periodic Fever Syndrome in Chinese Shar-Pei Dogs
Článek Polycomb Repressive Complex 2 Controls the Embryo-to-Seedling Phase Transition
Článek A Role for Set1/MLL-Related Components in Epigenetic Regulation of the Germ Line
Článek Genome-Wide Association Analysis Identifies Variants Associated with Nonalcoholic Fatty Liver Disease That Have Distinct Effects on Metabolic Traits
Článek A Genome-Wide Association Study of Upper Aerodigestive Tract Cancers Conducted within the INHANCE Consortium
Článek Ancestral Mutation in Telomerase Causes Defects in Repeat Addition Processivity and Manifests As Familial Pulmonary Fibrosis
Článek Ultra-Deep Sequencing of Mouse Mitochondrial DNA: Mutational Patterns and Their Origins
Článek Phenotype Restricted Genome-Wide Association Study Using a Gene-Centric Approach Identifies Three Low-Risk Neuroblastoma Susceptibility Loci
Článek The Toll-Like Receptor Gene Family Is Integrated into Human DNA Damage and p53 Networks
Článek Polycomb Targets Seek Closest Neighbours
Článek Widespread Hypomethylation Occurs Early and Synergizes with Gene Amplification during Esophageal Carcinogenesis
Článek c-di-GMP Turn-Over in Is Controlled by a Plethora of Diguanylate Cyclases and Phosphodiesterases
Článek Estimating Divergence Time and Ancestral Effective Population Size of Bornean and Sumatran Orangutan Subspecies Using a Coalescent Hidden Markov Model
Článek Rif1 Supports the Function of the CST Complex in Yeast Telomere Capping
Článek A Tradeoff Drives the Evolution of Reduced Metal Resistance in Natural Populations of Yeast
Článek Quantifying the Underestimation of Relative Risks from Genome-Wide Association Studies
Článek Population-Based Resequencing of Experimentally Evolved Populations Reveals the Genetic Basis of Body Size Variation in
Článek Triplet Repeat–Derived siRNAs Enhance RNA–Mediated Toxicity in a Drosophila Model for Myotonic Dystrophy
Článek The FUN30 Chromatin Remodeler, Fft3, Protects Centromeric and Subtelomeric Domains from Euchromatin Formation
Článek Viral Genome Segmentation Can Result from a Trade-Off between Genetic Content and Particle Stability
Článek Environmental Sex Determination in the Branchiopod Crustacean : Deep Conservation of a Gene in the Sex-Determining Pathway
Článek Systematic Detection of Polygenic Regulatory Evolution
Článek The SUMO Isopeptidase Ulp2p Is Required to Prevent Recombination-Induced Chromosome Segregation Lethality following DNA Replication Stress
Článek Uncoupling Antisense-Mediated Silencing and DNA Methylation in the Imprinted Cluster
Článek Role of the Drosophila Non-Visual ß-Arrestin Kurtz in Hedgehog Signalling
Článek COMPASS-Like Complexes Mediate Histone H3 Lysine-4 Trimethylation to Control Floral Transition and Plant Development
Článek H3 Lysine 4 Is Acetylated at Active Gene Promoters and Is Regulated by H3 Lysine 4 Methylation
Článek Diverse Roles and Interactions of the SWI/SNF Chromatin Remodeling Complex Revealed Using Global Approaches
Článek A Bow-Tie Genetic Architecture for Morphogenesis Suggested by a Genome-Wide RNAi Screen in
Článek Roles of () in Oocyte Nuclear Architecture, Gametogenesis, Gonad Tumors, and Genome Stability in Zebrafish
Článek A Molecular Phylogeny of Living Primates
Článek Roles of the Espin Actin-Bundling Proteins in the Morphogenesis and Stabilization of Hair Cell Stereocilia Revealed in CBA/CaJ Congenic Jerker Mice
Článek A Cholinergic-Regulated Circuit Coordinates the Maintenance and Bi-Stable States of a Sensory-Motor Behavior during Male Copulation
Článok vyšiel v časopise

PLOS Genetics

2011 Číslo 3
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

nový kurz
Autori: doc. MUDr. David Zemánek, Ph.D., MUDr. Anna Chaloupka, Ph.D.
Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#