Association of rs3135500 and rs3135499 Polymorphisms in the MicroRNA-binding Site of Nucleotide-binding Oligomerization Domain 2 (NOD2) Gene with Susceptibility to Rheumatoid Arthritis

The nucleotide-binding oligomerization domain 2 (NOD2) is the key regulator of inflammatory responses and has been involved in the pathogenesis of rheumatoid arthritis (RA). Laboratory and in silico evaluations have demonstrated that some polymorphisms in 3ˊUTR of NOD2 gene could influence the secon...

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Main Authors: Naeim Ehtesham, Behrang Alani, Deniz Mortazavi, Sara Azhdari, Taiebe Kenarangi, Emran Esmaeilzadeh, Bahram Pakzad
Format: Article
Language:English
Published: Tehran University of Medical Sciences 2021-04-01
Series:Iranian Journal of Allergy, Asthma and Immunology
Subjects:
Online Access:https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3094
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author Naeim Ehtesham
Behrang Alani
Deniz Mortazavi
Sara Azhdari
Taiebe Kenarangi
Emran Esmaeilzadeh
Bahram Pakzad
author_facet Naeim Ehtesham
Behrang Alani
Deniz Mortazavi
Sara Azhdari
Taiebe Kenarangi
Emran Esmaeilzadeh
Bahram Pakzad
author_sort Naeim Ehtesham
collection DOAJ
description The nucleotide-binding oligomerization domain 2 (NOD2) is the key regulator of inflammatory responses and has been involved in the pathogenesis of rheumatoid arthritis (RA). Laboratory and in silico evaluations have demonstrated that some polymorphisms in 3ˊUTR of NOD2 gene could influence the secondary structure of this region and similarly thermodynamic features of hybridization site and finally deregulate the expression of NOD2. In the current study, for the first time, we evaluated the possible association between single nucleotide polymorphisms (SNPs) rs3135500 and rs3135499 in the NOD2 gene with RA risk in the Iranian population. One hundred and fifteen patients with RA and 120 healthy subjects were recruited in this case-control study. Genotyping of rs3135500 and rs3135499 polymorphisms were accomplished using the real‑time polymerase chain reaction high resolution melting (HRM) method. We found a substantial association of AA and AG genotypes in rs3135500 with the risk of RA (AA vs GG; OR=5.547; 95%CI [2.564-11.999]; p<0.001 and AG vs GG; OR=2.179; 95%CI [1.145-4.147]; p=0.017). Moreover, in the patient group, there was a significant relationship between the increased concentration of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) with rs3135500 (A allele) (p<0.05). However, there were no important associations between rs3135499 with the risk of RA (p>0.05). However, we found a noteworthy association of the C allele in rs3135499 with an increased level of CRP in patients (p>0.05). Our findings propose a considerable association between NOD2 polymorphisms with increased risk of RA and disease activity.
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spelling doaj.art-0ab6cbed0f4e4653bcc28e3e6cf8894c2022-12-21T23:44:12ZengTehran University of Medical SciencesIranian Journal of Allergy, Asthma and Immunology1735-15021735-52492021-04-0120210.18502/ijaai.v20i2.6051Association of rs3135500 and rs3135499 Polymorphisms in the MicroRNA-binding Site of Nucleotide-binding Oligomerization Domain 2 (NOD2) Gene with Susceptibility to Rheumatoid ArthritisNaeim Ehtesham0Behrang Alani1Deniz Mortazavi2Sara Azhdari3Taiebe Kenarangi4Emran Esmaeilzadeh5Bahram Pakzad6Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-communicable Disease, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran AND Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, IranDepartment of Applied Cell Sciences, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, IranPediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-communicable Disease, School of Medicine, Isfahan University of Medical Sciences, Isfahan, IranDepartment of Anatomy and Embryology, School of Medicine, Bam University of Medical Sciences, Bam, IranStudent Research Committee, Faculty of Statistics, University of Social Welfare and Rehabilitation Science, Tehran, IranSchool of Medicine, AJA University of Medical Science, Tehran, IranDepartment of Internal Medicine, Division of Rheumatology, School of Medicine, Isfahan University of Medical Science, Isfahan, IranThe nucleotide-binding oligomerization domain 2 (NOD2) is the key regulator of inflammatory responses and has been involved in the pathogenesis of rheumatoid arthritis (RA). Laboratory and in silico evaluations have demonstrated that some polymorphisms in 3ˊUTR of NOD2 gene could influence the secondary structure of this region and similarly thermodynamic features of hybridization site and finally deregulate the expression of NOD2. In the current study, for the first time, we evaluated the possible association between single nucleotide polymorphisms (SNPs) rs3135500 and rs3135499 in the NOD2 gene with RA risk in the Iranian population. One hundred and fifteen patients with RA and 120 healthy subjects were recruited in this case-control study. Genotyping of rs3135500 and rs3135499 polymorphisms were accomplished using the real‑time polymerase chain reaction high resolution melting (HRM) method. We found a substantial association of AA and AG genotypes in rs3135500 with the risk of RA (AA vs GG; OR=5.547; 95%CI [2.564-11.999]; p<0.001 and AG vs GG; OR=2.179; 95%CI [1.145-4.147]; p=0.017). Moreover, in the patient group, there was a significant relationship between the increased concentration of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) with rs3135500 (A allele) (p<0.05). However, there were no important associations between rs3135499 with the risk of RA (p>0.05). However, we found a noteworthy association of the C allele in rs3135499 with an increased level of CRP in patients (p>0.05). Our findings propose a considerable association between NOD2 polymorphisms with increased risk of RA and disease activity.https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3094InflammationPolymorphismRheumatoid arthritis
spellingShingle Naeim Ehtesham
Behrang Alani
Deniz Mortazavi
Sara Azhdari
Taiebe Kenarangi
Emran Esmaeilzadeh
Bahram Pakzad
Association of rs3135500 and rs3135499 Polymorphisms in the MicroRNA-binding Site of Nucleotide-binding Oligomerization Domain 2 (NOD2) Gene with Susceptibility to Rheumatoid Arthritis
Iranian Journal of Allergy, Asthma and Immunology
Inflammation
Polymorphism
Rheumatoid arthritis
title Association of rs3135500 and rs3135499 Polymorphisms in the MicroRNA-binding Site of Nucleotide-binding Oligomerization Domain 2 (NOD2) Gene with Susceptibility to Rheumatoid Arthritis
title_full Association of rs3135500 and rs3135499 Polymorphisms in the MicroRNA-binding Site of Nucleotide-binding Oligomerization Domain 2 (NOD2) Gene with Susceptibility to Rheumatoid Arthritis
title_fullStr Association of rs3135500 and rs3135499 Polymorphisms in the MicroRNA-binding Site of Nucleotide-binding Oligomerization Domain 2 (NOD2) Gene with Susceptibility to Rheumatoid Arthritis
title_full_unstemmed Association of rs3135500 and rs3135499 Polymorphisms in the MicroRNA-binding Site of Nucleotide-binding Oligomerization Domain 2 (NOD2) Gene with Susceptibility to Rheumatoid Arthritis
title_short Association of rs3135500 and rs3135499 Polymorphisms in the MicroRNA-binding Site of Nucleotide-binding Oligomerization Domain 2 (NOD2) Gene with Susceptibility to Rheumatoid Arthritis
title_sort association of rs3135500 and rs3135499 polymorphisms in the microrna binding site of nucleotide binding oligomerization domain 2 nod2 gene with susceptibility to rheumatoid arthritis
topic Inflammation
Polymorphism
Rheumatoid arthritis
url https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3094
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