Next-generation sequencing of prolidase gene identifies novel and common variants associated with low prolidase in coronary artery ectasia
Background Decreased collagen biosynthesis and increased collagenolysis can cause ectasia progression in the arterial walls. Prolidase is a key enzyme in collagen synthesis; a decrease in prolidase activity or level may decrease collagen biosynthesis, which may contribute to ectasia formation. Consi...
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| Veröffentlicht in: | Molecular biology reports 2023-02, Vol.50 (2), p.1349-1365 |
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| creator | Pekkoc-Uyanik, Kubra Cigdem Aslan, Ezgi Irmak Kilicarslan, Onur Ser, Ozgur Selim Ozyildirim, Serhan Yanar, Fatih Yildiz, Ahmet Ozturk, Oguz Yilmaz-Aydogan, Hulya |
| description | Background
Decreased collagen biosynthesis and increased collagenolysis can cause ectasia progression in the arterial walls. Prolidase is a key enzyme in collagen synthesis; a decrease in prolidase activity or level may decrease collagen biosynthesis, which may contribute to ectasia formation. Considering that, the variations in
PEPD
gene encoding prolidase enzyme were evaluated by analyzing next-generation sequencing (NGS) for the first time together with known risk factors in coronary artery ectasia (CAE) patients.
Methods
Molecular analysis of the
PEPD
gene was performed on genomic DNA by NGS in 76 CAE patients and 76 controls. The serum levels of prolidase were measured by the sandwich-ELISA technique.
Results
Serum prolidase levels were significantly lower in CAE group compared to control group, and it was significantly lower in males than females in both groups (
p
|
| doi_str_mv | 10.1007/s11033-022-08142-1 |
| format | Article |
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Decreased collagen biosynthesis and increased collagenolysis can cause ectasia progression in the arterial walls. Prolidase is a key enzyme in collagen synthesis; a decrease in prolidase activity or level may decrease collagen biosynthesis, which may contribute to ectasia formation. Considering that, the variations in
PEPD
gene encoding prolidase enzyme were evaluated by analyzing next-generation sequencing (NGS) for the first time together with known risk factors in coronary artery ectasia (CAE) patients.
Methods
Molecular analysis of the
PEPD
gene was performed on genomic DNA by NGS in 76 CAE patients and 76 controls. The serum levels of prolidase were measured by the sandwich-ELISA technique.
Results
Serum prolidase levels were significantly lower in CAE group compared to control group, and it was significantly lower in males than females in both groups (
p
< 0.001). On the other hand, elevated prolidase levels were observed in CAE patients in the presence of diabetes (
p
< 0.001), hypertension (
p
< 0.05) and hyperlipidemia (
p
< 0.05). Logistic regression analysis demonstrated that the low prolidase level (
p
< 0.001), hypertension (
p
< 0.02) and hyperlipidemia (
p
< 0.012) were significantly associated with increased CAE risk. We identified four missense mutations in the
PEPD
gene, namely G296S, T266A, P365L and S134C (novel) that could be associated with CAE. The pathogenicity of these mutations was predicted to be “damaging” for G296S, S134C and P365L, but “benign” for T266A. We also identified a novel 5′UTR variation (Chr19:34012748 G>A) in one patient who had a low prolidase level. In addition, rs17570 and rs1061338 common variations of the
PEPD
gene were associated with low prolidase levels in CAE patients, while rs17569 variation was associated with high prolidase levels in both CAE and controls (
p
< 0.05).
Conclusions
Our findings indicate that the low serum prolidase levels observed in CAE patients is significantly associated with
PEPD
gene variations. It was concluded that low serum prolidase level and associated
PEPD
mutations may be potential biomarkers for the diagnosis of CAE.]]></description><identifier>ISSN: 0301-4851</identifier><identifier>EISSN: 1573-4978</identifier><identifier>DOI: 10.1007/s11033-022-08142-1</identifier><identifier>PMID: 36462085</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>5' Untranslated Regions ; Animal Anatomy ; Animal Biochemistry ; biomarkers ; Biomedical and Life Sciences ; Biosynthesis ; blood serum ; Collagen ; Coronary Angiography - methods ; Coronary artery ; Coronary Artery Disease - genetics ; Coronary Vessels ; diabetes ; Diabetes mellitus ; Dilatation, Pathologic ; DNA ; Enzyme-linked immunosorbent assay ; Enzymes ; Female ; genes ; High-Throughput Nucleotide Sequencing ; Histology ; Humans ; Hyperlipidemia ; Hyperlipidemias ; Hypertension ; Life Sciences ; Male ; Missense mutation ; Morphology ; Mutation ; Next-generation sequencing ; Original Article ; Pathogenicity ; patients ; Prolidase ; proline dipeptidase ; regression analysis ; risk ; Risk factors ; Serum levels ; Sex differences ; Variation</subject><ispartof>Molecular biology reports, 2023-02, Vol.50 (2), p.1349-1365</ispartof><rights>The Author(s), under exclusive licence to Springer Nature B.V. 2022. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2022. The Author(s), under exclusive licence to Springer Nature B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c338t-c2d249e52ca710738a4f42bc4c0cf3d6594a7d49a0eb8dfaa1a7c8ab44cd79b73</citedby><cites>FETCH-LOGICAL-c338t-c2d249e52ca710738a4f42bc4c0cf3d6594a7d49a0eb8dfaa1a7c8ab44cd79b73</cites><orcidid>0000-0001-5869-5536 ; 0000-0003-1399-3382 ; 0000-0002-8837-6664 ; 0000-0001-6676-5311 ; 0000-0002-5232-1100 ; 0000-0002-1056-960X ; 0000-0002-9205-5708 ; 0000-0001-9477-0740 ; 0000-0002-2439-9269</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11033-022-08142-1$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11033-022-08142-1$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36462085$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pekkoc-Uyanik, Kubra Cigdem</creatorcontrib><creatorcontrib>Aslan, Ezgi Irmak</creatorcontrib><creatorcontrib>Kilicarslan, Onur</creatorcontrib><creatorcontrib>Ser, Ozgur Selim</creatorcontrib><creatorcontrib>Ozyildirim, Serhan</creatorcontrib><creatorcontrib>Yanar, Fatih</creatorcontrib><creatorcontrib>Yildiz, Ahmet</creatorcontrib><creatorcontrib>Ozturk, Oguz</creatorcontrib><creatorcontrib>Yilmaz-Aydogan, Hulya</creatorcontrib><title>Next-generation sequencing of prolidase gene identifies novel and common variants associated with low prolidase in coronary artery ectasia</title><title>Molecular biology reports</title><addtitle>Mol Biol Rep</addtitle><addtitle>Mol Biol Rep</addtitle><description><![CDATA[Background
Decreased collagen biosynthesis and increased collagenolysis can cause ectasia progression in the arterial walls. Prolidase is a key enzyme in collagen synthesis; a decrease in prolidase activity or level may decrease collagen biosynthesis, which may contribute to ectasia formation. Considering that, the variations in
PEPD
gene encoding prolidase enzyme were evaluated by analyzing next-generation sequencing (NGS) for the first time together with known risk factors in coronary artery ectasia (CAE) patients.
Methods
Molecular analysis of the
PEPD
gene was performed on genomic DNA by NGS in 76 CAE patients and 76 controls. The serum levels of prolidase were measured by the sandwich-ELISA technique.
Results
Serum prolidase levels were significantly lower in CAE group compared to control group, and it was significantly lower in males than females in both groups (
p
< 0.001). On the other hand, elevated prolidase levels were observed in CAE patients in the presence of diabetes (
p
< 0.001), hypertension (
p
< 0.05) and hyperlipidemia (
p
< 0.05). Logistic regression analysis demonstrated that the low prolidase level (
p
< 0.001), hypertension (
p
< 0.02) and hyperlipidemia (
p
< 0.012) were significantly associated with increased CAE risk. We identified four missense mutations in the
PEPD
gene, namely G296S, T266A, P365L and S134C (novel) that could be associated with CAE. The pathogenicity of these mutations was predicted to be “damaging” for G296S, S134C and P365L, but “benign” for T266A. We also identified a novel 5′UTR variation (Chr19:34012748 G>A) in one patient who had a low prolidase level. In addition, rs17570 and rs1061338 common variations of the
PEPD
gene were associated with low prolidase levels in CAE patients, while rs17569 variation was associated with high prolidase levels in both CAE and controls (
p
< 0.05).
Conclusions
Our findings indicate that the low serum prolidase levels observed in CAE patients is significantly associated with
PEPD
gene variations. It was concluded that low serum prolidase level and associated
PEPD
mutations may be potential biomarkers for the diagnosis of CAE.]]></description><subject>5' Untranslated Regions</subject><subject>Animal Anatomy</subject><subject>Animal Biochemistry</subject><subject>biomarkers</subject><subject>Biomedical and Life Sciences</subject><subject>Biosynthesis</subject><subject>blood serum</subject><subject>Collagen</subject><subject>Coronary Angiography - methods</subject><subject>Coronary artery</subject><subject>Coronary Artery Disease - genetics</subject><subject>Coronary Vessels</subject><subject>diabetes</subject><subject>Diabetes mellitus</subject><subject>Dilatation, Pathologic</subject><subject>DNA</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Enzymes</subject><subject>Female</subject><subject>genes</subject><subject>High-Throughput Nucleotide Sequencing</subject><subject>Histology</subject><subject>Humans</subject><subject>Hyperlipidemia</subject><subject>Hyperlipidemias</subject><subject>Hypertension</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Missense mutation</subject><subject>Morphology</subject><subject>Mutation</subject><subject>Next-generation sequencing</subject><subject>Original Article</subject><subject>Pathogenicity</subject><subject>patients</subject><subject>Prolidase</subject><subject>proline dipeptidase</subject><subject>regression analysis</subject><subject>risk</subject><subject>Risk factors</subject><subject>Serum levels</subject><subject>Sex 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Selim</creator><creator>Ozyildirim, Serhan</creator><creator>Yanar, Fatih</creator><creator>Yildiz, Ahmet</creator><creator>Ozturk, Oguz</creator><creator>Yilmaz-Aydogan, Hulya</creator><general>Springer Netherlands</general><general>Springer Nature 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sequencing of prolidase gene identifies novel and common variants associated with low prolidase in coronary artery ectasia</title><author>Pekkoc-Uyanik, Kubra Cigdem ; Aslan, Ezgi Irmak ; Kilicarslan, Onur ; Ser, Ozgur Selim ; Ozyildirim, Serhan ; Yanar, Fatih ; Yildiz, Ahmet ; Ozturk, Oguz ; Yilmaz-Aydogan, Hulya</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c338t-c2d249e52ca710738a4f42bc4c0cf3d6594a7d49a0eb8dfaa1a7c8ab44cd79b73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>5' Untranslated Regions</topic><topic>Animal Anatomy</topic><topic>Animal Biochemistry</topic><topic>biomarkers</topic><topic>Biomedical and Life Sciences</topic><topic>Biosynthesis</topic><topic>blood serum</topic><topic>Collagen</topic><topic>Coronary Angiography - methods</topic><topic>Coronary artery</topic><topic>Coronary Artery Disease - genetics</topic><topic>Coronary Vessels</topic><topic>diabetes</topic><topic>Diabetes mellitus</topic><topic>Dilatation, Pathologic</topic><topic>DNA</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Enzymes</topic><topic>Female</topic><topic>genes</topic><topic>High-Throughput Nucleotide Sequencing</topic><topic>Histology</topic><topic>Humans</topic><topic>Hyperlipidemia</topic><topic>Hyperlipidemias</topic><topic>Hypertension</topic><topic>Life Sciences</topic><topic>Male</topic><topic>Missense mutation</topic><topic>Morphology</topic><topic>Mutation</topic><topic>Next-generation sequencing</topic><topic>Original Article</topic><topic>Pathogenicity</topic><topic>patients</topic><topic>Prolidase</topic><topic>proline dipeptidase</topic><topic>regression analysis</topic><topic>risk</topic><topic>Risk factors</topic><topic>Serum levels</topic><topic>Sex differences</topic><topic>Variation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pekkoc-Uyanik, Kubra Cigdem</creatorcontrib><creatorcontrib>Aslan, Ezgi Irmak</creatorcontrib><creatorcontrib>Kilicarslan, Onur</creatorcontrib><creatorcontrib>Ser, Ozgur Selim</creatorcontrib><creatorcontrib>Ozyildirim, Serhan</creatorcontrib><creatorcontrib>Yanar, Fatih</creatorcontrib><creatorcontrib>Yildiz, Ahmet</creatorcontrib><creatorcontrib>Ozturk, Oguz</creatorcontrib><creatorcontrib>Yilmaz-Aydogan, Hulya</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database 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biology reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pekkoc-Uyanik, Kubra Cigdem</au><au>Aslan, Ezgi Irmak</au><au>Kilicarslan, Onur</au><au>Ser, Ozgur Selim</au><au>Ozyildirim, Serhan</au><au>Yanar, Fatih</au><au>Yildiz, Ahmet</au><au>Ozturk, Oguz</au><au>Yilmaz-Aydogan, Hulya</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Next-generation sequencing of prolidase gene identifies novel and common variants associated with low prolidase in coronary artery ectasia</atitle><jtitle>Molecular biology reports</jtitle><stitle>Mol Biol Rep</stitle><addtitle>Mol Biol Rep</addtitle><date>2023-02-01</date><risdate>2023</risdate><volume>50</volume><issue>2</issue><spage>1349</spage><epage>1365</epage><pages>1349-1365</pages><issn>0301-4851</issn><eissn>1573-4978</eissn><abstract><![CDATA[Background
Decreased collagen biosynthesis and increased collagenolysis can cause ectasia progression in the arterial walls. Prolidase is a key enzyme in collagen synthesis; a decrease in prolidase activity or level may decrease collagen biosynthesis, which may contribute to ectasia formation. Considering that, the variations in
PEPD
gene encoding prolidase enzyme were evaluated by analyzing next-generation sequencing (NGS) for the first time together with known risk factors in coronary artery ectasia (CAE) patients.
Methods
Molecular analysis of the
PEPD
gene was performed on genomic DNA by NGS in 76 CAE patients and 76 controls. The serum levels of prolidase were measured by the sandwich-ELISA technique.
Results
Serum prolidase levels were significantly lower in CAE group compared to control group, and it was significantly lower in males than females in both groups (
p
< 0.001). On the other hand, elevated prolidase levels were observed in CAE patients in the presence of diabetes (
p
< 0.001), hypertension (
p
< 0.05) and hyperlipidemia (
p
< 0.05). Logistic regression analysis demonstrated that the low prolidase level (
p
< 0.001), hypertension (
p
< 0.02) and hyperlipidemia (
p
< 0.012) were significantly associated with increased CAE risk. We identified four missense mutations in the
PEPD
gene, namely G296S, T266A, P365L and S134C (novel) that could be associated with CAE. The pathogenicity of these mutations was predicted to be “damaging” for G296S, S134C and P365L, but “benign” for T266A. We also identified a novel 5′UTR variation (Chr19:34012748 G>A) in one patient who had a low prolidase level. In addition, rs17570 and rs1061338 common variations of the
PEPD
gene were associated with low prolidase levels in CAE patients, while rs17569 variation was associated with high prolidase levels in both CAE and controls (
p
< 0.05).
Conclusions
Our findings indicate that the low serum prolidase levels observed in CAE patients is significantly associated with
PEPD
gene variations. It was concluded that low serum prolidase level and associated
PEPD
mutations may be potential biomarkers for the diagnosis of CAE.]]></abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>36462085</pmid><doi>10.1007/s11033-022-08142-1</doi><tpages>17</tpages><orcidid>https://orcid.org/0000-0001-5869-5536</orcidid><orcidid>https://orcid.org/0000-0003-1399-3382</orcidid><orcidid>https://orcid.org/0000-0002-8837-6664</orcidid><orcidid>https://orcid.org/0000-0001-6676-5311</orcidid><orcidid>https://orcid.org/0000-0002-5232-1100</orcidid><orcidid>https://orcid.org/0000-0002-1056-960X</orcidid><orcidid>https://orcid.org/0000-0002-9205-5708</orcidid><orcidid>https://orcid.org/0000-0001-9477-0740</orcidid><orcidid>https://orcid.org/0000-0002-2439-9269</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0301-4851 |
| ispartof | Molecular biology reports, 2023-02, Vol.50 (2), p.1349-1365 |
| issn | 0301-4851 1573-4978 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2849900918 |
| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | 5' Untranslated Regions Animal Anatomy Animal Biochemistry biomarkers Biomedical and Life Sciences Biosynthesis blood serum Collagen Coronary Angiography - methods Coronary artery Coronary Artery Disease - genetics Coronary Vessels diabetes Diabetes mellitus Dilatation, Pathologic DNA Enzyme-linked immunosorbent assay Enzymes Female genes High-Throughput Nucleotide Sequencing Histology Humans Hyperlipidemia Hyperlipidemias Hypertension Life Sciences Male Missense mutation Morphology Mutation Next-generation sequencing Original Article Pathogenicity patients Prolidase proline dipeptidase regression analysis risk Risk factors Serum levels Sex differences Variation |
| title | Next-generation sequencing of prolidase gene identifies novel and common variants associated with low prolidase in coronary artery ectasia |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T02%3A25%3A40IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Next-generation%20sequencing%20of%20prolidase%20gene%20identifies%20novel%20and%20common%20variants%20associated%20with%20low%20prolidase%20in%20coronary%20artery%20ectasia&rft.jtitle=Molecular%20biology%20reports&rft.au=Pekkoc-Uyanik,%20Kubra%20Cigdem&rft.date=2023-02-01&rft.volume=50&rft.issue=2&rft.spage=1349&rft.epage=1365&rft.pages=1349-1365&rft.issn=0301-4851&rft.eissn=1573-4978&rft_id=info:doi/10.1007/s11033-022-08142-1&rft_dat=%3Cproquest_cross%3E2746394127%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2771189383&rft_id=info:pmid/36462085&rfr_iscdi=true |