Variable Association of Reactive Intermediate Genes with Systemic Lupus Erythematosus in Populations with Different African Ancestry

Objective.Little is known about the genetic etiology of systemic lupus erythematosus (SLE) in individuals of African ancestry, despite its higher prevalence and greater disease severity. Overproduction of nitric oxide (NO) and reactive oxygen species are implicated in the pathogenesis and severity of SLE, making NO synthases and other reactive intermediate-related genes biological candidates for disease susceptibility. We analyzed variation in reactive intermediate genes for association with SLE in 2 populations with African ancestry.Methods.A total of 244 single-nucleotide polymorphisms (SNP) from 53 regions were analyzed in non-Gullah African Americans (AA; 1432 cases and 1687 controls) and the genetically more homogeneous Gullah of the Sea Islands of South Carolina (133 cases and 112 controls). Single-marker, haplotype, and 2-locus interaction tests were computed for these populations.Results.The glutathione reductase gene GSR (rs2253409; p = 0.0014, OR 1.26, 95% CI 1.09–1.44) was the most significant single SNP association in AA. In the Gullah, the NADH dehydrogenase NDUFS4 (rs381575; p = 0.0065, OR 2.10, 95% CI 1.23–3.59) and NO synthase gene NOS1 (rs561712; p = 0.0072, OR 0.62, 95% CI 0.44–0.88) were most strongly associated with SLE. When both populations were analyzed together, GSR remained the most significant effect (rs2253409; p = 0.00072, OR 1.26, 95% CI 1.10–1.44). Haplotype and 2-locus interaction analyses also uncovered different loci in each population.Conclusion.These results suggest distinct patterns of association with SLE in African-derived populations; specific loci may be more strongly associated within select population groups.

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Variation in the ICAM1–ICAM4–ICAM5 locus is associated with systemic lupus erythematosus susceptibility in multiple ancestries

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2011-201110 ◽

2012 ◽

Vol 71 (11) ◽

pp. 1809-1814 ◽

Cited By ~ 43

Author(s):

Kwangwoo Kim ◽

Elizabeth E Brown ◽

Chan-Bum Choi ◽

Marta E Alarcón-Riquelme ◽

Jennifer A Kelly ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Large Scale ◽

Meta Analysis ◽

Gene Interaction ◽

Nucleotide Polymorphisms ◽

Systemic Lupus ◽

Intracellular Adhesion Molecule ◽

Single Marker ◽

Genetic And Environmental Factors

ObjectiveSystemic lupus erythematosus (SLE; OMIM 152700) is a chronic autoimmune disease for which the aetiology includes genetic and environmental factors. ITGAM, integrin αM (complement component 3 receptor 3 subunit) encoding a ligand for intracellular adhesion molecule (ICAM) proteins, is an established SLE susceptibility locus. This study aimed to evaluate the independent and joint effects of genetic variations in the genes that encode ITGAM and ICAM.MethodsThe authors examined several markers in the ICAM1–ICAM4–ICAM5 locus on chromosome 19p13 and the single ITGAM polymorphism (rs1143679) using a large-scale case–control study of 17 481 unrelated participants from four ancestry populations. The single-marker association and gene–gene interaction were analysed for each ancestry, and a meta-analysis across the four ancestries was performed.ResultsThe A-allele of ICAM1–ICAM4–ICAM5 rs3093030, associated with elevated plasma levels of soluble ICAM1, and the A-allele of ITGAM rs1143679 showed the strongest association with increased SLE susceptibility in each of the ancestry populations and the trans-ancestry meta-analysis (ORmeta=1.16, 95% CI 1.11 to 1.22; p=4.88×10−10 and ORmeta=1.67, 95% CI 1.55 to 1.79; p=3.32×10−46, respectively). The effect of the ICAM single-nucleotide polymorphisms (SNPs) was independent of the effect of the ITGAM SNP rs1143679, and carriers of both ICAM rs3093030-AA and ITGAM rs1143679-AA had an OR of 4.08 compared with those with no risk allele in either SNP (95% CI 2.09 to 7.98; p=3.91×10−5).ConclusionThese findings are the first to suggest that an ICAM–integrin-mediated pathway contributes to susceptibility to SLE.

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Analysis of C1q polymorphisms suggests association with systemic lupus erythematosus, serum C1q and CH50 levels and disease severity

Annals of the Rheumatic Diseases ◽

10.1136/ard.2007.085688 ◽

2008 ◽

Vol 68 (5) ◽

pp. 715-720 ◽

Cited By ~ 37

Author(s):

H A Martens ◽

M W Zuurman ◽

A H M de Lange ◽

I M Nolte ◽

G van der Steege ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Haplotype Analysis ◽

Damage Index ◽

Nucleotide Polymorphisms ◽

Founder Population ◽

Systemic Lupus ◽

Tag Snps ◽

Snp Association ◽

Low Serum

Background:Several findings link systemic lupus erythematosus (SLE) with C1q, the first molecule of the classical complement pathway. Polymorphisms of the C1qA gene are associated with low serum C1q levels in patients with cutaneous LE, but C1q polymorphisms have not been studied in patients with systemic lupus.Objective:To determine whether polymorphisms of the C1q genes are associated with SLE, disease phenotypes, serum C1q and CH50 levels.Methods:DNA for genetic analysis was obtained from 103 Caucasian patients with SLE and their family members. Five tag single nucleotide polymorphisms (tag SNPs) served as unique markers for underlying SNPs in the genes of the C1q protein. The pedigree disequilibrium test (PDT) was applied to trios to determine association of markers with SLE, SLE phenotypes, low serum C1q and low CH50. Single SNP association and haplotype analysis was also performed.Results:The PDT revealed a significant association of the tag SNP rs631090 (covering the C1qB gene) with SLE (p = 0.02). Rs631090 was moderately associated with low serum C1q levels (p = 0.06). In addition, the tag SNPs rs292001 and rs294183 were associated with more severe SLE (Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) damage index score>0; p = 0.007 and p = 0.02, respectively). Haplotype analysis and single SNP association analysis showed no significant associations, but additional analyses revealed that marker rs587585 is associated with low serum C1q and CH50 levels.Conclusions:C1q polymorphisms are associated with SLE, serum C1q and CH50 levels in a stable founder population of patients with SLE. Although the studied population was small and allele frequencies were low, this is the first study to suggest an association of C1q polymorphisms with SLE.

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Variable Association of Reactive Intermediate Genes with Systemic Lupus Erythematosus in Populations with Different African Ancestry

The Journal of Rheumatology ◽

10.3899/jrheum.120989.c1 ◽

2013 ◽

Vol 40 (7) ◽

pp. 1240.3-1240

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

African Ancestry ◽

Reactive Intermediate ◽

Systemic Lupus

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EMBRACE: Phase 3/4, Randomized, 52‐Week Study of Belimumab Efficacy and Safety in Patients of Black African Ancestry With Systemic Lupus Erythematosus

Arthritis & Rheumatology ◽

10.1002/art.41900 ◽

2021 ◽

Author(s):

Ellen Ginzler ◽

Luiz Sergio Guedes Barbosa ◽

David D’Cruz ◽

Richard Furie ◽

Kathleen Maksimowicz‐McKinnon ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

African Ancestry ◽

Efficacy And Safety ◽

Systemic Lupus ◽

Phase 3 ◽

Black African

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Association of interleukin-2 and interferon-γ single nucleotide polymorphisms with Juvenile systemic lupus erythematosus

Allergologia et Immunopathologia ◽

10.1016/j.aller.2015.12.005 ◽

2016 ◽

Vol 44 (5) ◽

pp. 422-426 ◽

Cited By ~ 5

Author(s):

S. Harsini ◽

V. Ziaee ◽

F. Tahghighi ◽

M. Mahmoudi ◽

A. Rezaei ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Single Nucleotide Polymorphisms ◽

Lupus Erythematosus ◽

Interleukin 2 ◽

Interferon Γ ◽

Nucleotide Polymorphisms ◽

Systemic Lupus ◽

Juvenile Systemic Lupus Erythematosus ◽

Single Nucleotide

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Cluster of highly expressed interferon-stimulated genes associate more with African ancestry than disease activity in patients with systemic lupus erythematosus. A systematic review of cross-sectional studies.

Translational Research ◽

10.1016/j.trsl.2021.07.006 ◽

2021 ◽

Author(s):

Kanwal Z. Siddiqi ◽

Theresa R. Wilhelm ◽

Constance J. Ulff-Møller ◽

Søren Jacobsen

Keyword(s):

Systematic Review ◽

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

African Ancestry ◽

Systemic Lupus ◽

Cross Sectional ◽

Interferon Stimulated Genes ◽

Cross Sectional Studies

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A case of generalized pustular psoriasis caused by hydroxychloroquine in a patient with systemic lupus erythematosus

Lupus ◽

10.1177/0961203319854139 ◽

2019 ◽

Vol 28 (8) ◽

pp. 1017-1020 ◽

Cited By ~ 5

Author(s):

E Shindo ◽

K Shikano ◽

M Kawazoe ◽

T Yamamoto ◽

N Kusunoki ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Neutrophil Infiltration ◽

Pustular Psoriasis ◽

Nucleotide Polymorphisms ◽

Systemic Lupus ◽

Single Nucleotide ◽

Potential Development ◽

Generalized Pustular Psoriasis ◽

The Face

Hydroxychloroquine (HCQ) has been used to treat systemic lupus erythematosus (SLE) in Japan since 2015. We herein report a case of SLE that developed generalized pustular psoriasis (GPP) following the administration of HCQ. Twenty-one days after the HCQ treatment, a pustular rash with itching appeared on the auricle, scalp, and forearm, and spread rapidly to the face and body trunk with a high fever and arthralgia. Skin biopsy showed pustule formation under the cornified layer, neutrophil infiltration, the destruction of keratinocytes, and spongiform pustules of Kogoj. The patient was diagnosed with GPP. HCQ was immediately discontinued, the dose of prednisolone (PSL) was increased, and granulocyte and monocyte adsorption apheresis was performed. Her symptoms subsequently disappeared. Since arthralgia relapsed after the tapering of PSL, cyclosporine was added. Although single nucleotide polymorphisms (c.28C>T and c.115+6T>C) in the interleukin (IL)-36RN gene, which encodes the IL-36 receptor antagonist, have frequently been reported in GPP, these mutations were not observed in the present case. The potential development of GPP needs to be considered when administering HCQ to patients with SLE.

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