Associations between eNOS polymorphisms and susceptibility to systemic lupus erythematosus and rheumatoid arthritis: a meta-analysis

Assoziationen zwischen eNOS-Polymorphismen und der Suszeptibilität für systemischen Lupus erythematodes und rheumatoide Arthritis: eine Metaanalyse

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Abstract

Objective

The aim of this study was to determine whether endothelial nitric oxide synthase (eNOS) polymorphisms are associated with susceptibility to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).

Methods

A meta-analysis was conducted on associations between the 4b/a, T786C, and G894T polymorphisms of eNOS and SLE or RA using the following methods: (1) allele contrast, (2) recessive model, (3) dominant model, and (4) homozygous contrast.

Results

Nineteen studies were included in this meta-analysis, comprising eleven studies on SLE (1561 patients and 1565 controls) and eight on RA (1624 patients and 2118 controls). Meta-analysis showed a significant association between SLE and the 4b/a polymorphism using the recessive model and the homozygous contrast (odds ratio [OR] = 1.836, 95 % confidence interval [CI] = 1.171–2.878, p = 0.008; OR = 2.055, 95 % CI = 1.302–3.243, p = 0.002). Ethnicity-specific meta-analysis showed a significant association between the aa vs. bb of the 4b/a polymorphism and SLE in European populations (OR = 2.096, 95 % CI = 1.288–4.0, p = 0.027), but not in Arab populations. Stratification by presence of lupus nephritis (LN) indicated a significant association between the a allele and the aa + ab genotype of the 4b/a polymorphism and LN in SLE patients (OR = 2.125, 95 % CI = 1.289–3.054, p = 0.003; OR = 2.655, 95 % CI = 1.509–4.671, p = 0.001). Meta-analysis indicated no association between SLE and the T786C and G894T polymorphisms. No association was found between the eNOS 4b/a, T786C, and G894T polymorphisms and RA

Conclusions

This meta-analysis of published studies shows that the eNOS 4b/a polymorphism may be associated with the development of SLE, but the 4b/a, T786C, and G894T polymorphisms may be not associated with RA susceptibility.

Zusammenfassung

Ziel

Ziel dieser Studie war es, festzustellen, ob Polymorphismen der endothelialen Stickstoffmonoxid-Synthase (eNOS) mit einer Suszeptibilität für systemischen Lupus erythematodes (SLE) und rheumatoide Arthritis (RA) assoziiert sind.

Methoden

Eine Metaanalyse wurde hinsichtlich der Assoziationen zwischen den eNOS-Polymorphismen 4b/a, T786C sowie G894T und SLE oder RA unter Verwendung der folgenden Methoden durchgeführt: (1) Allel-Kontrast-Modell, (2) rezessives Modell, (3) dominantes Modell und (4) homozygotes Kontrast-Modell.

Ergebnisse

Neunzehn Studien wurden in diese Metaanalyse eingeschlossen, die 11 SLE-Studien (1561 Patienten und 1565 Kontrollpersonen) und 8 RA-Studien (1624 Patienten und 2118 Kontrollpersonen) umfasste. Die Metaanalyse zeigte eine signifikante Assoziation zwischen SLE und dem 4b/a-Polymorphismus unter Anwendung des rezessiven und des homozygoten Kontrast-Modells (Odds-Ratio [OR] = 1,836, 95 % Konfidenzintervall [CI] = 1,171–2,878; p = 0,008; OR = 2,055, 95 % CI = 1,302–3,243; p = 0,002).

Eine ethnizitätsbezogene Metaanalyse zeigte eine signifikante Assoziation zwischen dem aa und dem bb des 4b/a-Polymorphismus und SLE in der europäischen Population (OR = 2,096, 95 % CI = 1,288–4,0; p = 0,027), jedoch nicht in der arabischen Population. Die Stratifizierung bei Vorliegen einer Lupusnephritis (LN) zeigte eine signifikante Assoziation zwischen dem a‑Allel und dem aa+ ab-Genotyp des 4b/a-Polymorphismus und LN bei SLE-Patienten (OR = 2,125, 95 % CI = 1,289–3,054; p = 0,003; OR = 2,655, 95 % CI = 1,509–4,671; p = 0,001). Die Metaanalyse zeigte keine Assoziation zwischen SLE und den Polymorphismen T786C und G894T. Es wurde keine Assoziation zwischen den eNOS-Polymorphismen 4b/a, T786C sowie G894T und RA gefunden.

Schlussfolgerungen

Diese Metaanalyse publizierter Studien zeigt, dass der eNOS-Polymorphismus 4a/b mit dem Entstehen eines SLE assoziiert sein könnte. Die Polymorphismen 4b/a, T786C sowie G894T sind jedoch vermutlich nicht mit einer Suszeptibilität für RA assoziiert.

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Acknowledgements

This study was supported in part by a grant of the Korea Healthcare technology R&D Project, Ministry for Health and Welfare, Republic of Korea (HI15C2958).

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Correspondence to Y. H. Lee PhD.

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Y.H. Lee and S.-C. Bae declare that they have no conflicts of interest.

The accompanying manuscript does not include studies on humans or animals performed by any of the authors.

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U. Müller-Ladner, Bad Nauheim

U. Lange, Bad Nauheim

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Lee, Y.H., Bae, S. Associations between eNOS polymorphisms and susceptibility to systemic lupus erythematosus and rheumatoid arthritis: a meta-analysis. Z Rheumatol 76, 708–715 (2017). https://doi.org/10.1007/s00393-016-0157-4

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Keywords

  • Systemic lupus erythematosus
  • Rheumatoid arthritis
  • Endothelial nitric oxide synthase
  • Polymorphism
  • Meta-analysis

Schlüsselwörter

  • Systemischer Lupus erythematodes
  • Rheumatoide Arthritis
  • Endotheliale Stickstoffmonoxid-Synthase
  • Polymorphismus
  • Metaanalyse