MICA and NLRP3 gene polymorphisms interact synergistically affecting the risk of ankylosing spondylitis
Ankylosing spondylitis (AS) is an autoinflammatory disease that affects the sacroiliac joints, causing stiffness and pain in the back. MICA is a ligand of the NKG2D receptor, and an increase in its expression affects the immune response in various diseases. NLRP3 is a multiprotein complex that promo...
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| Veröffentlicht in: | Immunologic research 2024-02, Vol.72 (1), p.119-127 |
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| description | Ankylosing spondylitis (AS) is an autoinflammatory disease that affects the sacroiliac joints, causing stiffness and pain in the back. MICA is a ligand of the NKG2D receptor, and an increase in its expression affects the immune response in various diseases. NLRP3 is a multiprotein complex that promotes the release of IL-1β, but its role in AS has been minimally explored. The objective of this study was to analyze the association and interaction of polymorphic variants of the
MICA
and
NLRP3
genes in patients with AS. In this case–control study, patients with AS were included and compared with healthy controls of Mexican origin. The polymorphisms rs4349859 and rs116488202 of
MICA
and rs3806268 and rs10754558 of
NLRP3
were genotyped using TaqMan probes. Associations were determined using logistic regression models, while interactions were analyzed by the multifactorial dimensionality reduction (MDR) method. A
P
value |
| doi_str_mv | 10.1007/s12026-023-09419-8 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_3153593123</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3153593123</sourcerecordid><originalsourceid>FETCH-LOGICAL-c359t-74d4c0eed5beb7feca01d27a51ae4aeaae39d7b6bbed608239b313f0f1fe21c03</originalsourceid><addsrcrecordid>eNqFkc1u1TAQRi0EopfCC7BAltiwCR3bsZ0sUcWfdCkIgcTOcpJJ6jaJgyd3kbevyy0gsSirkTxnzoz1MfZcwGsBYM9ISJCmAKkKqEtRF9UDthNa1wVYrR-yHUhtC2ntjxP2hOgKQJiyVI_ZibLG6Azu2PDp4_kb7ueOX-y_flF8wBn5Esdtimm5DDQRD_OKybcrp23GNARaQ-vHceO-77Fdwzzw9RJ5CnTNY59d19sY6faZljh32xjWQE_Zo96PhM_u6in7_u7tt_MPxf7z-3zBvmiVrtfCll3ZAmKnG2xs1nsQnbReC4-lR-9R1Z1tTNNgZ6CSqm6UUD30okcpWlCn7NXRu6T484C0uilQi-PoZ4wHckrovEgJqf6LysqAEbY0NqMv_0Gv4iHN-SNO1qIqQVS1yJQ8Um2KRAl7t6Qw-bQ5Ae42MXdMzOXE3K_EXJWHXtypD82E3Z-R3xFlQB0Byq15wPR39z3aGztiopU</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2918401891</pqid></control><display><type>article</type><title>MICA and NLRP3 gene polymorphisms interact synergistically affecting the risk of ankylosing spondylitis</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><creator>Fernández-Torres, Javier ; Zamudio-Cuevas, Yessica ; Ruiz-Dávila, Xiadani ; López-Macay, Ambar ; Martínez-Flores, Karina</creator><creatorcontrib>Fernández-Torres, Javier ; Zamudio-Cuevas, Yessica ; Ruiz-Dávila, Xiadani ; López-Macay, Ambar ; Martínez-Flores, Karina</creatorcontrib><description>Ankylosing spondylitis (AS) is an autoinflammatory disease that affects the sacroiliac joints, causing stiffness and pain in the back. MICA is a ligand of the NKG2D receptor, and an increase in its expression affects the immune response in various diseases. NLRP3 is a multiprotein complex that promotes the release of IL-1β, but its role in AS has been minimally explored. The objective of this study was to analyze the association and interaction of polymorphic variants of the
MICA
and
NLRP3
genes in patients with AS. In this case–control study, patients with AS were included and compared with healthy controls of Mexican origin. The polymorphisms rs4349859 and rs116488202 of
MICA
and rs3806268 and rs10754558 of
NLRP3
were genotyped using TaqMan probes. Associations were determined using logistic regression models, while interactions were analyzed by the multifactorial dimensionality reduction (MDR) method. A
P
value < 0.05 was considered statistically significant. The minor allele of rs4349859 (A) and rs116488202 (T) of
MICA
polymorphisms showed risk associations with AS (OR = 9.22, 95% CI = 4.26–20.0,
P
< 0.001; OR = 9.36, 95% CI = 4.17–21.0,
P
< 0.001), while the minor allele of the rs3806268 (A) polymorphism of
NLRP3
was associated with protection (OR = 0.55, 95% CI = 0.33–0.91,
P
= 0.019). MDR analysis revealed synergistic interactions between the
MICA
and
NLRP3
polymorphisms (
P
= 0.012). In addition, high- and low-risk genotypes were identified among these variants. The study findings suggest that the
MICA
rs4349859 A allele and rs116488202 T allele are associated with AS risk. An interaction between
MICA
and
NLRP3
was observed which could increase the genetic risk in AS.</description><identifier>ISSN: 0257-277X</identifier><identifier>EISSN: 1559-0755</identifier><identifier>DOI: 10.1007/s12026-023-09419-8</identifier><identifier>PMID: 37665559</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Alleles ; Allergology ; Ankylosing spondylitis ; Arthritis ; Biomedical and Life Sciences ; Biomedicine ; Case-Control Studies ; Gene polymorphism ; Genetic Predisposition to Disease ; Genotype ; Genotypes ; genotyping ; Humans ; Immune response ; Immunology ; Inflammatory diseases ; Internal Medicine ; ligands ; Medicine/Public Health ; multiprotein complexes ; NLR Family, Pyrin Domain-Containing 3 Protein - genetics ; Original Article ; pain ; Polymorphism ; Polymorphism, Single Nucleotide ; Regression analysis ; Risk ; Spondylitis, Ankylosing - genetics ; Statistical analysis</subject><ispartof>Immunologic research, 2024-02, Vol.72 (1), p.119-127</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023. 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>2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c359t-74d4c0eed5beb7feca01d27a51ae4aeaae39d7b6bbed608239b313f0f1fe21c03</cites><orcidid>0000-0003-3023-3326 ; 0000-0002-7271-2862 ; 0000-0002-2916-7424 ; 0000-0003-1751-3454 ; 0000-0003-0675-0227</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/s12026-023-09419-8$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12026-023-09419-8$$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/37665559$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fernández-Torres, Javier</creatorcontrib><creatorcontrib>Zamudio-Cuevas, Yessica</creatorcontrib><creatorcontrib>Ruiz-Dávila, Xiadani</creatorcontrib><creatorcontrib>López-Macay, Ambar</creatorcontrib><creatorcontrib>Martínez-Flores, Karina</creatorcontrib><title>MICA and NLRP3 gene polymorphisms interact synergistically affecting the risk of ankylosing spondylitis</title><title>Immunologic research</title><addtitle>Immunol Res</addtitle><addtitle>Immunol Res</addtitle><description>Ankylosing spondylitis (AS) is an autoinflammatory disease that affects the sacroiliac joints, causing stiffness and pain in the back. MICA is a ligand of the NKG2D receptor, and an increase in its expression affects the immune response in various diseases. NLRP3 is a multiprotein complex that promotes the release of IL-1β, but its role in AS has been minimally explored. The objective of this study was to analyze the association and interaction of polymorphic variants of the
MICA
and
NLRP3
genes in patients with AS. In this case–control study, patients with AS were included and compared with healthy controls of Mexican origin. The polymorphisms rs4349859 and rs116488202 of
MICA
and rs3806268 and rs10754558 of
NLRP3
were genotyped using TaqMan probes. Associations were determined using logistic regression models, while interactions were analyzed by the multifactorial dimensionality reduction (MDR) method. A
P
value < 0.05 was considered statistically significant. The minor allele of rs4349859 (A) and rs116488202 (T) of
MICA
polymorphisms showed risk associations with AS (OR = 9.22, 95% CI = 4.26–20.0,
P
< 0.001; OR = 9.36, 95% CI = 4.17–21.0,
P
< 0.001), while the minor allele of the rs3806268 (A) polymorphism of
NLRP3
was associated with protection (OR = 0.55, 95% CI = 0.33–0.91,
P
= 0.019). MDR analysis revealed synergistic interactions between the
MICA
and
NLRP3
polymorphisms (
P
= 0.012). In addition, high- and low-risk genotypes were identified among these variants. The study findings suggest that the
MICA
rs4349859 A allele and rs116488202 T allele are associated with AS risk. An interaction between
MICA
and
NLRP3
was observed which could increase the genetic risk in AS.</description><subject>Alleles</subject><subject>Allergology</subject><subject>Ankylosing spondylitis</subject><subject>Arthritis</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Case-Control Studies</subject><subject>Gene polymorphism</subject><subject>Genetic Predisposition to Disease</subject><subject>Genotype</subject><subject>Genotypes</subject><subject>genotyping</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immunology</subject><subject>Inflammatory diseases</subject><subject>Internal Medicine</subject><subject>ligands</subject><subject>Medicine/Public Health</subject><subject>multiprotein complexes</subject><subject>NLR Family, Pyrin Domain-Containing 3 Protein - genetics</subject><subject>Original Article</subject><subject>pain</subject><subject>Polymorphism</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Regression analysis</subject><subject>Risk</subject><subject>Spondylitis, Ankylosing - genetics</subject><subject>Statistical analysis</subject><issn>0257-277X</issn><issn>1559-0755</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1u1TAQRi0EopfCC7BAltiwCR3bsZ0sUcWfdCkIgcTOcpJJ6jaJgyd3kbevyy0gsSirkTxnzoz1MfZcwGsBYM9ISJCmAKkKqEtRF9UDthNa1wVYrR-yHUhtC2ntjxP2hOgKQJiyVI_ZibLG6Azu2PDp4_kb7ueOX-y_flF8wBn5Esdtimm5DDQRD_OKybcrp23GNARaQ-vHceO-77Fdwzzw9RJ5CnTNY59d19sY6faZljh32xjWQE_Zo96PhM_u6in7_u7tt_MPxf7z-3zBvmiVrtfCll3ZAmKnG2xs1nsQnbReC4-lR-9R1Z1tTNNgZ6CSqm6UUD30okcpWlCn7NXRu6T484C0uilQi-PoZ4wHckrovEgJqf6LysqAEbY0NqMv_0Gv4iHN-SNO1qIqQVS1yJQ8Um2KRAl7t6Qw-bQ5Ae42MXdMzOXE3K_EXJWHXtypD82E3Z-R3xFlQB0Byq15wPR39z3aGztiopU</recordid><startdate>20240201</startdate><enddate>20240201</enddate><creator>Fernández-Torres, Javier</creator><creator>Zamudio-Cuevas, Yessica</creator><creator>Ruiz-Dávila, Xiadani</creator><creator>López-Macay, Ambar</creator><creator>Martínez-Flores, Karina</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><orcidid>https://orcid.org/0000-0003-3023-3326</orcidid><orcidid>https://orcid.org/0000-0002-7271-2862</orcidid><orcidid>https://orcid.org/0000-0002-2916-7424</orcidid><orcidid>https://orcid.org/0000-0003-1751-3454</orcidid><orcidid>https://orcid.org/0000-0003-0675-0227</orcidid></search><sort><creationdate>20240201</creationdate><title>MICA and NLRP3 gene polymorphisms interact synergistically affecting the risk of ankylosing spondylitis</title><author>Fernández-Torres, Javier ; Zamudio-Cuevas, Yessica ; Ruiz-Dávila, Xiadani ; López-Macay, Ambar ; Martínez-Flores, Karina</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c359t-74d4c0eed5beb7feca01d27a51ae4aeaae39d7b6bbed608239b313f0f1fe21c03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Alleles</topic><topic>Allergology</topic><topic>Ankylosing spondylitis</topic><topic>Arthritis</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Case-Control Studies</topic><topic>Gene polymorphism</topic><topic>Genetic Predisposition to Disease</topic><topic>Genotype</topic><topic>Genotypes</topic><topic>genotyping</topic><topic>Humans</topic><topic>Immune response</topic><topic>Immunology</topic><topic>Inflammatory diseases</topic><topic>Internal Medicine</topic><topic>ligands</topic><topic>Medicine/Public Health</topic><topic>multiprotein complexes</topic><topic>NLR Family, Pyrin Domain-Containing 3 Protein - genetics</topic><topic>Original Article</topic><topic>pain</topic><topic>Polymorphism</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Regression analysis</topic><topic>Risk</topic><topic>Spondylitis, Ankylosing - genetics</topic><topic>Statistical analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fernández-Torres, Javier</creatorcontrib><creatorcontrib>Zamudio-Cuevas, Yessica</creatorcontrib><creatorcontrib>Ruiz-Dávila, Xiadani</creatorcontrib><creatorcontrib>López-Macay, Ambar</creatorcontrib><creatorcontrib>Martínez-Flores, Karina</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><jtitle>Immunologic research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fernández-Torres, Javier</au><au>Zamudio-Cuevas, Yessica</au><au>Ruiz-Dávila, Xiadani</au><au>López-Macay, Ambar</au><au>Martínez-Flores, Karina</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MICA and NLRP3 gene polymorphisms interact synergistically affecting the risk of ankylosing spondylitis</atitle><jtitle>Immunologic research</jtitle><stitle>Immunol Res</stitle><addtitle>Immunol Res</addtitle><date>2024-02-01</date><risdate>2024</risdate><volume>72</volume><issue>1</issue><spage>119</spage><epage>127</epage><pages>119-127</pages><issn>0257-277X</issn><eissn>1559-0755</eissn><abstract>Ankylosing spondylitis (AS) is an autoinflammatory disease that affects the sacroiliac joints, causing stiffness and pain in the back. MICA is a ligand of the NKG2D receptor, and an increase in its expression affects the immune response in various diseases. NLRP3 is a multiprotein complex that promotes the release of IL-1β, but its role in AS has been minimally explored. The objective of this study was to analyze the association and interaction of polymorphic variants of the
MICA
and
NLRP3
genes in patients with AS. In this case–control study, patients with AS were included and compared with healthy controls of Mexican origin. The polymorphisms rs4349859 and rs116488202 of
MICA
and rs3806268 and rs10754558 of
NLRP3
were genotyped using TaqMan probes. Associations were determined using logistic regression models, while interactions were analyzed by the multifactorial dimensionality reduction (MDR) method. A
P
value < 0.05 was considered statistically significant. The minor allele of rs4349859 (A) and rs116488202 (T) of
MICA
polymorphisms showed risk associations with AS (OR = 9.22, 95% CI = 4.26–20.0,
P
< 0.001; OR = 9.36, 95% CI = 4.17–21.0,
P
< 0.001), while the minor allele of the rs3806268 (A) polymorphism of
NLRP3
was associated with protection (OR = 0.55, 95% CI = 0.33–0.91,
P
= 0.019). MDR analysis revealed synergistic interactions between the
MICA
and
NLRP3
polymorphisms (
P
= 0.012). In addition, high- and low-risk genotypes were identified among these variants. The study findings suggest that the
MICA
rs4349859 A allele and rs116488202 T allele are associated with AS risk. An interaction between
MICA
and
NLRP3
was observed which could increase the genetic risk in AS.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>37665559</pmid><doi>10.1007/s12026-023-09419-8</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-3023-3326</orcidid><orcidid>https://orcid.org/0000-0002-7271-2862</orcidid><orcidid>https://orcid.org/0000-0002-2916-7424</orcidid><orcidid>https://orcid.org/0000-0003-1751-3454</orcidid><orcidid>https://orcid.org/0000-0003-0675-0227</orcidid></addata></record> |
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| subjects | Alleles Allergology Ankylosing spondylitis Arthritis Biomedical and Life Sciences Biomedicine Case-Control Studies Gene polymorphism Genetic Predisposition to Disease Genotype Genotypes genotyping Humans Immune response Immunology Inflammatory diseases Internal Medicine ligands Medicine/Public Health multiprotein complexes NLR Family, Pyrin Domain-Containing 3 Protein - genetics Original Article pain Polymorphism Polymorphism, Single Nucleotide Regression analysis Risk Spondylitis, Ankylosing - genetics Statistical analysis |
| title | MICA and NLRP3 gene polymorphisms interact synergistically affecting the risk of ankylosing spondylitis |
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