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Strong association of common variants in the miRNA-binding site of NOD2 gene with clinicopathological characteristics and disease activity of systemic lupus erythematosus

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Abstract

Introduction/objectives

Systemic lupus erythematosus (SLE) is a multifactorial systemic autoimmune disease, in which genetic susceptibility plays a pivotal role. The nucleotide oligomerization domain 2 (NOD2) gene is one of the main regulators of chronic inflammatory conditions and could be involved in SLE pathogenesis. Single nucleotide polymorphisms (SNPs) in miRNA binding sites which are located in 3′UTR of the NOD2 gene could be associated with SLE risk by dysregulation of NOD2 expression. In the present study, we assessed the possible association between SNPs rs3135500 and rs3135499 in the NOD2 gene with SLE risk in the Iranian population.

Methods

A case–control study using 110 SLE patients and 120 control subjects was undertaken to estimate rs3135500 (G > A) and rs3135499 (A > C) genotypes via real-time PCR high-resolution melting method (HRM).

Results

No significant association was observed between allele and genotype frequencies of rs3135500 and rs3135499 polymorphisms and SLE risk in this population (P > 0.05). However, there was an obvious association between rs3135500 (A allele) with laboratory factors that are associated with disease activity (P < 0.05) and some clinical manifestations that are associated with disease severity such as neurological symptoms, skin manifestations, renal involvements, and higher serum concentration of creatinine (P < 0.05). Besides, rs3135499 (C allele) was correlated with renal involvement and also the concentration of creatinine (P < 0.05). Moreover, in the patients group, the risk alleles in these polymorphisms were associated with lower age of onset (P < 0.05).

Conclusions

Our results suggest a substantial association between NOD2 polymorphisms with clinicopathological characteristics and SLE disease activity.

Key Points

• Single nucleotide polymorphisms (SNPs) in miRNA binding sites which are located in 3′UTR of the NOD2 gene could be associated with SLE risk by dysregulation of NOD2 expression.

• Our results suggested that two miRSNPs (rs3135500 and rs3135499) in the NOD2 gene were meaningfully correlated with clinicopathological characteristics and disease activity of SLE.

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Acknowledgements

We would like to appreciate any support provided by Isfahan University of Medical Sciences and AJA University of Medical Science.

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Authors and Affiliations

  1. School of Medicine, AJA University of Medical Science, Tehran, Iran

    Emran Esmaeilzadeh, Mostafa Saghi, Mehdi Hassani & Mehrdad Nasrollahzadeh Sabet

  2. Department of Epidemiology and Biostatistics, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran

    Saeideh Davar

  3. Department of Applied Cell Sciences, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran

    Behrang Alani

  4. Division of Rheumatology, Department of Internal Medicine, School of Medicine, Isfahan University of Medical Science, Isfahan, Iran

    Bahram Pakzad

  5. Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non Communicable Disease, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

    Sepideh Ghobakhloo & Sharifeh Khosravi

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  1. Emran Esmaeilzadeh
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Correspondence to Mehrdad Nasrollahzadeh Sabet.

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Esmaeilzadeh, E., Saghi, M., Hassani, M. et al. Strong association of common variants in the miRNA-binding site of NOD2 gene with clinicopathological characteristics and disease activity of systemic lupus erythematosus. Clin Rheumatol 40, 4559–4567 (2021). https://doi.org/10.1007/s10067-021-05812-6

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