HLA Class III: A susceptibility region to systemic lupus erythematosus in Tunisian population
Short tandem repeats (STR) are usually used as informative polymorphic markers for genetic mapping and for disease susceptibility analysis. The involvement of these microsatellite markers localized in the MHC region was reported in many auto-immune diseases. In this study we analyzed for the first t...
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| creator | Hachicha, Hend Mahfoudh, Nadia Fourati, Hajer Elloumi, Nesrine Marzouk, Sameh Feki, Sawsan Fakhfakh, Raouia Frikha, Faten Ayadi, Abir Maatoug, Amira Gaddour, Lilia Hakim, Feiza Bahloul, Zouheir Makni, Hafedh Masmoudi, Hatem Kammoun, Arwa |
| description | Short tandem repeats (STR) are usually used as informative polymorphic markers for genetic mapping and for disease susceptibility analysis. The involvement of these microsatellite markers localized in the MHC region was reported in many auto-immune diseases. In this study we analyzed for the first time eight polymorphisms of microsatellite loci at the HLA region: D6S291, D6S273, TNFa, b and c, MICA, D6S265 and D6S276, in Tunisian systemic lupus erythematosus (SLE) patients.
We performed a case control study in which the microsatellite loci were amplified using specific primers labeled with NED, VIC, PET or 6-FAM and analyzed using GeneScan software 3.7. For the statistical analysis, we used SPSS software and we performed a sub-haplotype scoring test using the haplo.stats software developed in the R language.
We found that two mean associated regions existed; the most statistically significant encompassed the 3 TNF markers (p = 0.0003, OR = 19.34); the latter covered the DR region. In fact, when scoring haplotypes in 3 marker- sliding windows, the p value increased as we moved away from the TNF region and decreased again when we approached the DRB1 locus. We also established for the first time the negative association between alleles of D6S291 and SLE. The majority of clinical and serological correlations were noted with TNF alleles.
Our results confirm the association between TNF and DRB1 polymorphisms and SLE. The association between alleles of D6S291 and SLE needs however to be verified by the analysis of other markers beyond this region. |
| doi_str_mv | 10.1371/journal.pone.0198549 |
| format | Article |
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We performed a case control study in which the microsatellite loci were amplified using specific primers labeled with NED, VIC, PET or 6-FAM and analyzed using GeneScan software 3.7. For the statistical analysis, we used SPSS software and we performed a sub-haplotype scoring test using the haplo.stats software developed in the R language.
We found that two mean associated regions existed; the most statistically significant encompassed the 3 TNF markers (p = 0.0003, OR = 19.34); the latter covered the DR region. In fact, when scoring haplotypes in 3 marker- sliding windows, the p value increased as we moved away from the TNF region and decreased again when we approached the DRB1 locus. We also established for the first time the negative association between alleles of D6S291 and SLE. The majority of clinical and serological correlations were noted with TNF alleles.
Our results confirm the association between TNF and DRB1 polymorphisms and SLE. The association between alleles of D6S291 and SLE needs however to be verified by the analysis of other markers beyond this region.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0198549</identifier><identifier>PMID: 29912900</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Alleles ; Antigens ; Arthritis ; Autoimmune diseases ; Biology and Life Sciences ; Case-Control Studies ; Chromosome mapping ; Chronic conditions ; Computer programs ; Diabetes ; Drb1 protein ; Female ; Gene mapping ; Genes ; Genetic analysis ; Genetic aspects ; Genetic markers ; Genetic Predisposition to Disease - genetics ; Haplotypes ; Histocompatibility antigen HLA ; HLA antigens ; HLA Antigens - genetics ; Hospitals ; Humans ; Immunological diseases ; Immunology ; Internal medicine ; Loci ; Lupus ; Lupus Erythematosus, Systemic - genetics ; Major histocompatibility complex ; Male ; Markers ; Medicine ; Medicine and Health Sciences ; MICA protein ; Microsatellite Repeats - genetics ; Microsatellites ; Middle Aged ; People and Places ; Polymorphism ; Polymorphism, Genetic - genetics ; Population ; Population (statistical) ; Primers ; Research and Analysis Methods ; Rheumatology ; Short tandem repeats ; Software ; Statistical analysis ; Systemic lupus erythematosus ; Tandem repeat sequences ; Tumor necrosis factor-α ; Tunisia - epidemiology ; Young Adult</subject><ispartof>PloS one, 2018-06, Vol.13 (6), p.e0198549-e0198549</ispartof><rights>COPYRIGHT 2018 Public Library of Science</rights><rights>2018 Hachicha et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2018 Hachicha et al 2018 Hachicha et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-37f6658f27e1731cae9f83aaba8f729bc8942384114ce0d4320307508ce5cea33</citedby><cites>FETCH-LOGICAL-c692t-37f6658f27e1731cae9f83aaba8f729bc8942384114ce0d4320307508ce5cea33</cites><orcidid>0000-0002-5819-2899</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6005577/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6005577/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29912900$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hachicha, Hend</creatorcontrib><creatorcontrib>Mahfoudh, Nadia</creatorcontrib><creatorcontrib>Fourati, Hajer</creatorcontrib><creatorcontrib>Elloumi, Nesrine</creatorcontrib><creatorcontrib>Marzouk, Sameh</creatorcontrib><creatorcontrib>Feki, Sawsan</creatorcontrib><creatorcontrib>Fakhfakh, Raouia</creatorcontrib><creatorcontrib>Frikha, Faten</creatorcontrib><creatorcontrib>Ayadi, Abir</creatorcontrib><creatorcontrib>Maatoug, Amira</creatorcontrib><creatorcontrib>Gaddour, Lilia</creatorcontrib><creatorcontrib>Hakim, Feiza</creatorcontrib><creatorcontrib>Bahloul, Zouheir</creatorcontrib><creatorcontrib>Makni, Hafedh</creatorcontrib><creatorcontrib>Masmoudi, Hatem</creatorcontrib><creatorcontrib>Kammoun, Arwa</creatorcontrib><title>HLA Class III: A susceptibility region to systemic lupus erythematosus in Tunisian population</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Short tandem repeats (STR) are usually used as informative polymorphic markers for genetic mapping and for disease susceptibility analysis. The involvement of these microsatellite markers localized in the MHC region was reported in many auto-immune diseases. In this study we analyzed for the first time eight polymorphisms of microsatellite loci at the HLA region: D6S291, D6S273, TNFa, b and c, MICA, D6S265 and D6S276, in Tunisian systemic lupus erythematosus (SLE) patients.
We performed a case control study in which the microsatellite loci were amplified using specific primers labeled with NED, VIC, PET or 6-FAM and analyzed using GeneScan software 3.7. For the statistical analysis, we used SPSS software and we performed a sub-haplotype scoring test using the haplo.stats software developed in the R language.
We found that two mean associated regions existed; the most statistically significant encompassed the 3 TNF markers (p = 0.0003, OR = 19.34); the latter covered the DR region. In fact, when scoring haplotypes in 3 marker- sliding windows, the p value increased as we moved away from the TNF region and decreased again when we approached the DRB1 locus. We also established for the first time the negative association between alleles of D6S291 and SLE. The majority of clinical and serological correlations were noted with TNF alleles.
Our results confirm the association between TNF and DRB1 polymorphisms and SLE. The association between alleles of D6S291 and SLE needs however to be verified by the analysis of other markers beyond this region.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Alleles</subject><subject>Antigens</subject><subject>Arthritis</subject><subject>Autoimmune diseases</subject><subject>Biology and Life Sciences</subject><subject>Case-Control Studies</subject><subject>Chromosome mapping</subject><subject>Chronic conditions</subject><subject>Computer programs</subject><subject>Diabetes</subject><subject>Drb1 protein</subject><subject>Female</subject><subject>Gene mapping</subject><subject>Genes</subject><subject>Genetic analysis</subject><subject>Genetic aspects</subject><subject>Genetic markers</subject><subject>Genetic Predisposition to Disease - genetics</subject><subject>Haplotypes</subject><subject>Histocompatibility antigen HLA</subject><subject>HLA antigens</subject><subject>HLA Antigens - genetics</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Immunological diseases</subject><subject>Immunology</subject><subject>Internal medicine</subject><subject>Loci</subject><subject>Lupus</subject><subject>Lupus Erythematosus, Systemic - genetics</subject><subject>Major histocompatibility complex</subject><subject>Male</subject><subject>Markers</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>MICA protein</subject><subject>Microsatellite Repeats - genetics</subject><subject>Microsatellites</subject><subject>Middle Aged</subject><subject>People and Places</subject><subject>Polymorphism</subject><subject>Polymorphism, Genetic - genetics</subject><subject>Population</subject><subject>Population (statistical)</subject><subject>Primers</subject><subject>Research and Analysis Methods</subject><subject>Rheumatology</subject><subject>Short tandem repeats</subject><subject>Software</subject><subject>Statistical analysis</subject><subject>Systemic lupus erythematosus</subject><subject>Tandem repeat sequences</subject><subject>Tumor necrosis factor-α</subject><subject>Tunisia - 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Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hachicha, Hend</au><au>Mahfoudh, Nadia</au><au>Fourati, Hajer</au><au>Elloumi, Nesrine</au><au>Marzouk, Sameh</au><au>Feki, Sawsan</au><au>Fakhfakh, Raouia</au><au>Frikha, Faten</au><au>Ayadi, Abir</au><au>Maatoug, Amira</au><au>Gaddour, Lilia</au><au>Hakim, Feiza</au><au>Bahloul, Zouheir</au><au>Makni, Hafedh</au><au>Masmoudi, Hatem</au><au>Kammoun, Arwa</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>HLA Class III: A susceptibility region to systemic lupus erythematosus in Tunisian population</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2018-06-18</date><risdate>2018</risdate><volume>13</volume><issue>6</issue><spage>e0198549</spage><epage>e0198549</epage><pages>e0198549-e0198549</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Short tandem repeats (STR) are usually used as informative polymorphic markers for genetic mapping and for disease susceptibility analysis. The involvement of these microsatellite markers localized in the MHC region was reported in many auto-immune diseases. In this study we analyzed for the first time eight polymorphisms of microsatellite loci at the HLA region: D6S291, D6S273, TNFa, b and c, MICA, D6S265 and D6S276, in Tunisian systemic lupus erythematosus (SLE) patients.
We performed a case control study in which the microsatellite loci were amplified using specific primers labeled with NED, VIC, PET or 6-FAM and analyzed using GeneScan software 3.7. For the statistical analysis, we used SPSS software and we performed a sub-haplotype scoring test using the haplo.stats software developed in the R language.
We found that two mean associated regions existed; the most statistically significant encompassed the 3 TNF markers (p = 0.0003, OR = 19.34); the latter covered the DR region. In fact, when scoring haplotypes in 3 marker- sliding windows, the p value increased as we moved away from the TNF region and decreased again when we approached the DRB1 locus. We also established for the first time the negative association between alleles of D6S291 and SLE. The majority of clinical and serological correlations were noted with TNF alleles.
Our results confirm the association between TNF and DRB1 polymorphisms and SLE. The association between alleles of D6S291 and SLE needs however to be verified by the analysis of other markers beyond this region.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>29912900</pmid><doi>10.1371/journal.pone.0198549</doi><tpages>e0198549</tpages><orcidid>https://orcid.org/0000-0002-5819-2899</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2018-06, Vol.13 (6), p.e0198549-e0198549 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2056823983 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Adolescent Adult Aged Aged, 80 and over Alleles Antigens Arthritis Autoimmune diseases Biology and Life Sciences Case-Control Studies Chromosome mapping Chronic conditions Computer programs Diabetes Drb1 protein Female Gene mapping Genes Genetic analysis Genetic aspects Genetic markers Genetic Predisposition to Disease - genetics Haplotypes Histocompatibility antigen HLA HLA antigens HLA Antigens - genetics Hospitals Humans Immunological diseases Immunology Internal medicine Loci Lupus Lupus Erythematosus, Systemic - genetics Major histocompatibility complex Male Markers Medicine Medicine and Health Sciences MICA protein Microsatellite Repeats - genetics Microsatellites Middle Aged People and Places Polymorphism Polymorphism, Genetic - genetics Population Population (statistical) Primers Research and Analysis Methods Rheumatology Short tandem repeats Software Statistical analysis Systemic lupus erythematosus Tandem repeat sequences Tumor necrosis factor-α Tunisia - epidemiology Young Adult |
| title | HLA Class III: A susceptibility region to systemic lupus erythematosus in Tunisian population |
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