Risk of relapse of ANCA-associated vasculitis among patients homozygous for the proteinase 3 gene Val119Ile polymorphism
© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ..
BACKGROUND: The frequency of proteinase 3 gene (PRTN3) polymorphisms in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is not fully characterised. We hypothesise that the presence of a PRTN3 gene polymorphism (single nucleotide polymorphism (SNP) rs351111) is relevant for clinical outcomes.
METHODS: DNA variant calling for SNP rs351111 (chr.19:844020, c.355G>A) in PRTN3 gene assessed the allelic frequency in patients with PR3-AAV included in the Rituximab in ANCA-Associated Vasculitis trial. This was followed by RNA-seq variant calling to characterise the mRNA expression. We compared clinical outcomes between patients homozygous for PRTN3-Ile119 or PRTN3-Val119.
RESULTS: Whole blood samples for DNA calling were available in 188 patients. 75 patients with PR3-AAV had the allelic variant: 62 heterozygous PRTN3-Val119Ile and 13 homozygous for PRTN3-Ile119. RNA-seq was available for 89 patients and mRNA corresponding to the allelic variant was found in 32 patients with PR3-AAV: 25 heterozygous PRTN3-Val119Ile and 7 homozygous for PRTN3-Ile119. The agreement between the DNA calling results and mRNA expression of the 86 patients analysed by both methods was 100%. We compared the clinical outcomes of 64 patients with PR3-AAV: 51 homozygous for PRTN3-Val119 and 13 homozygous for PRTN3-Ile119. The frequency of severe flares at 18 months in homozygous PRTN3-Ile119 was significantly higher when compared with homozygous PRTN3-Val119 (46.2% vs 19.6%, p=0.048). Multivariate analysis identified homozygous PR3-Ile119 as main predictor of severe relapse (HR 4.67, 95% CI 1.16 to 18.86, p=0.030).
CONCLUSION: In patients with PR3-AAV, homozygosity for PRTN3-Val119Ile polymorphism appears associated with higher frequency of severe relapse. Further studies are necessary to better understand the association of this observation with the risk of severe relapse.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2023 |
---|---|
Erschienen: |
2023 |
Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
---|---|
Enthalten in: |
RMD open - 9(2023), 1 vom: 11. März |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Casal Moura, Marta [VerfasserIn] |
---|
Links: |
---|
Anmerkungen: |
Date Completed 31.03.2023 Date Revised 12.04.2024 published: Print Citation Status MEDLINE |
---|
doi: |
10.1136/rmdopen-2022-002935 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM354955993 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | NLM354955993 | ||
003 | DE-627 | ||
005 | 20240412232401.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231226s2023 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1136/rmdopen-2022-002935 |2 doi | |
028 | 5 | 2 | |a pubmed24n1373.xml |
035 | |a (DE-627)NLM354955993 | ||
035 | |a (NLM)36990659 | ||
035 | |a (PII)e002935 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Casal Moura, Marta |e verfasserin |4 aut | |
245 | 1 | 0 | |a Risk of relapse of ANCA-associated vasculitis among patients homozygous for the proteinase 3 gene Val119Ile polymorphism |
264 | 1 | |c 2023 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 31.03.2023 | ||
500 | |a Date Revised 12.04.2024 | ||
500 | |a published: Print | ||
500 | |a Citation Status MEDLINE | ||
520 | |a © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. | ||
520 | |a BACKGROUND: The frequency of proteinase 3 gene (PRTN3) polymorphisms in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is not fully characterised. We hypothesise that the presence of a PRTN3 gene polymorphism (single nucleotide polymorphism (SNP) rs351111) is relevant for clinical outcomes | ||
520 | |a METHODS: DNA variant calling for SNP rs351111 (chr.19:844020, c.355G>A) in PRTN3 gene assessed the allelic frequency in patients with PR3-AAV included in the Rituximab in ANCA-Associated Vasculitis trial. This was followed by RNA-seq variant calling to characterise the mRNA expression. We compared clinical outcomes between patients homozygous for PRTN3-Ile119 or PRTN3-Val119 | ||
520 | |a RESULTS: Whole blood samples for DNA calling were available in 188 patients. 75 patients with PR3-AAV had the allelic variant: 62 heterozygous PRTN3-Val119Ile and 13 homozygous for PRTN3-Ile119. RNA-seq was available for 89 patients and mRNA corresponding to the allelic variant was found in 32 patients with PR3-AAV: 25 heterozygous PRTN3-Val119Ile and 7 homozygous for PRTN3-Ile119. The agreement between the DNA calling results and mRNA expression of the 86 patients analysed by both methods was 100%. We compared the clinical outcomes of 64 patients with PR3-AAV: 51 homozygous for PRTN3-Val119 and 13 homozygous for PRTN3-Ile119. The frequency of severe flares at 18 months in homozygous PRTN3-Ile119 was significantly higher when compared with homozygous PRTN3-Val119 (46.2% vs 19.6%, p=0.048). Multivariate analysis identified homozygous PR3-Ile119 as main predictor of severe relapse (HR 4.67, 95% CI 1.16 to 18.86, p=0.030) | ||
520 | |a CONCLUSION: In patients with PR3-AAV, homozygosity for PRTN3-Val119Ile polymorphism appears associated with higher frequency of severe relapse. Further studies are necessary to better understand the association of this observation with the risk of severe relapse | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a Research Support, N.I.H., Extramural | |
650 | 4 | |a Autoantibodies | |
650 | 4 | |a Granulomatosis with polyangiitis | |
650 | 4 | |a Outcome Assessment, Health Care | |
650 | 4 | |a Polymorphism, Genetic | |
650 | 4 | |a Systemic vasculitis | |
650 | 7 | |a Myeloblastin |2 NLM | |
650 | 7 | |a EC 3.4.21.76 |2 NLM | |
650 | 7 | |a Antibodies, Antineutrophil Cytoplasmic |2 NLM | |
700 | 1 | |a Deng, Zuoming |e verfasserin |4 aut | |
700 | 1 | |a Brooks, Stephen R |e verfasserin |4 aut | |
700 | 1 | |a Tew, Wei |e verfasserin |4 aut | |
700 | 1 | |a Fervenza, Fernando C |e verfasserin |4 aut | |
700 | 1 | |a Kallenberg, Cees G M |e verfasserin |4 aut | |
700 | 1 | |a Langford, Carol A |e verfasserin |4 aut | |
700 | 1 | |a Merkel, Peter A |e verfasserin |4 aut | |
700 | 1 | |a Monach, Paul A |e verfasserin |4 aut | |
700 | 1 | |a Seo, Philip |e verfasserin |4 aut | |
700 | 1 | |a Spiera, Robert F |e verfasserin |4 aut | |
700 | 1 | |a St Clair, E William |e verfasserin |4 aut | |
700 | 1 | |a Stone, John H |e verfasserin |4 aut | |
700 | 1 | |a Prunotto, Marco |e verfasserin |4 aut | |
700 | 1 | |a Grayson, Peter C |e verfasserin |4 aut | |
700 | 1 | |a Specks, Ulrich |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t RMD open |d 2015 |g 9(2023), 1 vom: 11. März |w (DE-627)NLM254089658 |x 2056-5933 |7 nnns |
773 | 1 | 8 | |g volume:9 |g year:2023 |g number:1 |g day:11 |g month:03 |
856 | 4 | 0 | |u http://dx.doi.org/10.1136/rmdopen-2022-002935 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 9 |j 2023 |e 1 |b 11 |c 03 |