Molecular Factors in PAD2 (PADI2) and PAD4 (PADI4) Are Associated with Interstitial Lung Disease Susceptibility in Rheumatoid Arthritis Patients Article Swipe
Karol J. Nava-Quiroz
,
Jorge Rojas‐Serrano
,
Gloría Pérez-Rubio
,
Ivette Buendía-Roldán
,
Mayra Mejía
,
Juan Carlos Fernández-López
,
Pedro Rodríguez‐Henríquez
,
Noé Ayala-Alcantar
,
Espiridión Ramos-Martı́nez
,
Luis A. López-Flores
,
Alma D. Del Ángel-Pablo
,
Ramcés Falfán‐Valencia
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.3390/cells12182235
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.3390/cells12182235
Around 50% of rheumatoid arthritis (RA) patients show some extra-articular manifestation, with the lung a usually affected organ; in addition, the presence of anti-citrullinated protein antibodies (ACPA) is a common feature, which is caused by protein citrullination modifications, catalyzed by the peptidyl arginine deiminases (PAD) enzymes. We aimed to identify single nucleotide variants (SNV) in PADI2 and PADI4 genes (PAD2 and PAD4 proteins, respectively) associated with susceptibility to interstitial lung disease (ILD) in RA patients and the PAD2 and PAD4 levels. Material and methods: 867 subjects were included: 118 RA-ILD patients, 133 RA patients, and 616 clinically healthy subjects (CHS). Allelic discrimination was performed in eight SNVs using qPCR, four in PADI2 and four in PADI4. The ELISA technique determined PAD2 and PAD4 levels in serum and bronchoalveolar lavage (BAL) samples, and the population structure was evaluated using 14 informative ancestry markers. Results: The rs1005753-GG (OR = 4.9) in PADI2 and rs11203366-AA (OR = 3.08), rs11203367-GG (OR = 2.4) in PADI4 are associated with genetic susceptibility to RA-ILD as well as the ACTC haplotype (OR = 2.64). In addition, the PAD4 protein is increased in RA-ILD individuals harboring the minor allele homozygous genotype in PADI4 SNVs. Moreover, rs1748033 in PADI4, rs2057094, and rs2076615 in PADI2 are associated with RA susceptibility. In conclusion, in RA patients, single nucleotide variants in PADI4 and PADI2 are associated with ILD susceptibility. The rs1748033 in PADI4 and two different SNVs in PADI2 are associated with RA development but not ILD. PAD4 serum levels are increased in RA-ILD patients.
Related Topics
Concepts
Citrullination
Medicine
Interstitial lung disease
Rheumatoid arthritis
Haplotype
Immunology
Allele frequency
Genotype
Lung
Internal medicine
Biology
Genetics
Gene
Citrulline
Arginine
Amino acid
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3390/cells12182235
- https://www.mdpi.com/2073-4409/12/18/2235/pdf?version=1694156593
- OA Status
- gold
- Cited By
- 12
- References
- 66
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4386541697
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4386541697Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3390/cells12182235Digital Object Identifier
- Title
-
Molecular Factors in PAD2 (PADI2) and PAD4 (PADI4) Are Associated with Interstitial Lung Disease Susceptibility in Rheumatoid Arthritis PatientsWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-09-08Full publication date if available
- Authors
-
Karol J. Nava-Quiroz, Jorge Rojas‐Serrano, Gloría Pérez-Rubio, Ivette Buendía-Roldán, Mayra Mejía, Juan Carlos Fernández-López, Pedro Rodríguez‐Henríquez, Noé Ayala-Alcantar, Espiridión Ramos-Martı́nez, Luis A. López-Flores, Alma D. Del Ángel-Pablo, Ramcés Falfán‐ValenciaList of authors in order
- Landing page
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https://doi.org/10.3390/cells12182235Publisher landing page
- PDF URL
-
https://www.mdpi.com/2073-4409/12/18/2235/pdf?version=1694156593Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.mdpi.com/2073-4409/12/18/2235/pdf?version=1694156593Direct OA link when available
- Concepts
-
Citrullination, Medicine, Interstitial lung disease, Rheumatoid arthritis, Haplotype, Immunology, Allele frequency, Genotype, Lung, Internal medicine, Biology, Genetics, Gene, Citrulline, Arginine, Amino acidTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
12Total citation count in OpenAlex
- Citations by year (recent)
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2025: 3, 2024: 7, 2023: 2Per-year citation counts (last 5 years)
- References (count)
-
66Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.133 | 91 |
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| abstract_inverted_index.(SNV) | 53 |
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| abstract_inverted_index.PADI4 | 57, 160, 194, 219, 230 |
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| abstract_inverted_index.3.08), | 154 |
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| corresponding_author_ids | https://openalex.org/A5007262185 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 12 |
| corresponding_institution_ids | https://openalex.org/I4210102695 |
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| sustainable_development_goals[0].display_name | Peace, Justice and strong institutions |
| citation_normalized_percentile.value | 0.93738473 |
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| citation_normalized_percentile.is_in_top_10_percent | True |