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Soluble HLA‐G levels in seminal plasma are associated with HLA‐G 3′UTR genotypes and haplotypes

Soluble HLA‐G (sHLA‐G) levels in human seminal plasma (SP) can be diverse and may affect the establishment of maternal‐fetal tolerance and thereby the outcome of pregnancy. We investigated whether sHLA‐G levels in SP are associated with polymorphisms in the 3′‐untranslated region (UTR) and UTR haplo...

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Published in:HLA : immune response genetics 2019-10, Vol.94 (4), p.339-346
Main Authors: Craenmehr, Moniek H. C., Haasnoot, Geert W., Drabbels, Jos J. M., Spruyt‐Gerritse, Marijke J., Cao, Milo, Keur, Carin, Kapsenberg, Johanna M., Uyar‐Mercankaya, Merve, Beelen, Els, Meuleman, Tess, Hoorn, Marie‐Louise P., Heidt, Sebastiaan, Claas, Frans H. J., Eikmans, Michael
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cited_by cdi_FETCH-LOGICAL-c3598-f80c547e074a82e94fa751d95c5096000de2718dcd8cdc5e30394cc310c672c3
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container_issue 4
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container_title HLA : immune response genetics
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creator Craenmehr, Moniek H. C.
Haasnoot, Geert W.
Drabbels, Jos J. M.
Spruyt‐Gerritse, Marijke J.
Cao, Milo
Keur, Carin
Kapsenberg, Johanna M.
Uyar‐Mercankaya, Merve
Beelen, Els
Meuleman, Tess
Hoorn, Marie‐Louise P.
Heidt, Sebastiaan
Claas, Frans H. J.
Eikmans, Michael
description Soluble HLA‐G (sHLA‐G) levels in human seminal plasma (SP) can be diverse and may affect the establishment of maternal‐fetal tolerance and thereby the outcome of pregnancy. We investigated whether sHLA‐G levels in SP are associated with polymorphisms in the 3′‐untranslated region (UTR) and UTR haplotypes of the HLA‐G gene. Furthermore, we compared the HLA‐G genotype distribution and sHLA‐G levels between men, whose partner experienced unexplained recurrent miscarriage (RM), and controls. Soluble HLA‐G levels (n = 156) and HLA‐G genotyping (n = 176) were determined in SP samples. The concentration of sHLA‐G was significantly associated with several single‐nucleotide polymorphisms (SNPs): the 14 base pair (bp) insertion/deletion (indel), +3010, +3142, +3187, +3196, and + 3509. High levels of sHLA‐G were associated with UTR‐1 and low levels with UTR‐2, UTR‐4, and UTR‐7 (P
doi_str_mv 10.1111/tan.13628
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C. ; Haasnoot, Geert W. ; Drabbels, Jos J. M. ; Spruyt‐Gerritse, Marijke J. ; Cao, Milo ; Keur, Carin ; Kapsenberg, Johanna M. ; Uyar‐Mercankaya, Merve ; Beelen, Els ; Meuleman, Tess ; Hoorn, Marie‐Louise P. ; Heidt, Sebastiaan ; Claas, Frans H. J. ; Eikmans, Michael</creator><creatorcontrib>Craenmehr, Moniek H. C. ; Haasnoot, Geert W. ; Drabbels, Jos J. M. ; Spruyt‐Gerritse, Marijke J. ; Cao, Milo ; Keur, Carin ; Kapsenberg, Johanna M. ; Uyar‐Mercankaya, Merve ; Beelen, Els ; Meuleman, Tess ; Hoorn, Marie‐Louise P. ; Heidt, Sebastiaan ; Claas, Frans H. J. ; Eikmans, Michael</creatorcontrib><description>Soluble HLA‐G (sHLA‐G) levels in human seminal plasma (SP) can be diverse and may affect the establishment of maternal‐fetal tolerance and thereby the outcome of pregnancy. We investigated whether sHLA‐G levels in SP are associated with polymorphisms in the 3′‐untranslated region (UTR) and UTR haplotypes of the HLA‐G gene. Furthermore, we compared the HLA‐G genotype distribution and sHLA‐G levels between men, whose partner experienced unexplained recurrent miscarriage (RM), and controls. Soluble HLA‐G levels (n = 156) and HLA‐G genotyping (n = 176) were determined in SP samples. The concentration of sHLA‐G was significantly associated with several single‐nucleotide polymorphisms (SNPs): the 14 base pair (bp) insertion/deletion (indel), +3010, +3142, +3187, +3196, and + 3509. High levels of sHLA‐G were associated with UTR‐1 and low levels with UTR‐2, UTR‐4, and UTR‐7 (P &lt; .0001). HLA‐G genotype distribution and sHLA‐G levels in SP were not significantly different between the RM group (n = 44) and controls (n = 31). In conclusion, seminal sHLA‐G levels are associated with both singular SNPs and 3UTR haplotypes. HLA‐G genotype and sHLA‐G levels in SP are not different between men whose partner experienced RM and controls, indicating that miscarriages are not solely the result of low sHLA‐G levels in SP. Instead, it is more likely that these miscarriages are the result of a multifactorial immunologic mechanism, whereby the HLA‐G 3′UTR 14 bp ins/ins genotype plays a role in a proportion of the cases. Future studies should look into the functions of sHLA‐G in SP and the consequences of low or high levels on the chance to conceive.</description><identifier>ISSN: 2059-2302</identifier><identifier>EISSN: 2059-2310</identifier><identifier>DOI: 10.1111/tan.13628</identifier><identifier>PMID: 31321883</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>immunology ; Original ; pregnancy ; recurrent miscarriage ; seminal plasma ; soluble HLA‐G</subject><ispartof>HLA : immune response genetics, 2019-10, Vol.94 (4), p.339-346</ispartof><rights>2019 The Authors. HLA: Immune Response Genetics published by John Wiley &amp; Sons Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3598-f80c547e074a82e94fa751d95c5096000de2718dcd8cdc5e30394cc310c672c3</citedby><cites>FETCH-LOGICAL-c3598-f80c547e074a82e94fa751d95c5096000de2718dcd8cdc5e30394cc310c672c3</cites><orcidid>0000-0002-9648-4227 ; 0000-0001-5505-8195</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids></links><search><creatorcontrib>Craenmehr, Moniek H. C.</creatorcontrib><creatorcontrib>Haasnoot, Geert W.</creatorcontrib><creatorcontrib>Drabbels, Jos J. M.</creatorcontrib><creatorcontrib>Spruyt‐Gerritse, Marijke J.</creatorcontrib><creatorcontrib>Cao, Milo</creatorcontrib><creatorcontrib>Keur, Carin</creatorcontrib><creatorcontrib>Kapsenberg, Johanna M.</creatorcontrib><creatorcontrib>Uyar‐Mercankaya, Merve</creatorcontrib><creatorcontrib>Beelen, Els</creatorcontrib><creatorcontrib>Meuleman, Tess</creatorcontrib><creatorcontrib>Hoorn, Marie‐Louise P.</creatorcontrib><creatorcontrib>Heidt, Sebastiaan</creatorcontrib><creatorcontrib>Claas, Frans H. J.</creatorcontrib><creatorcontrib>Eikmans, Michael</creatorcontrib><title>Soluble HLA‐G levels in seminal plasma are associated with HLA‐G 3′UTR genotypes and haplotypes</title><title>HLA : immune response genetics</title><description>Soluble HLA‐G (sHLA‐G) levels in human seminal plasma (SP) can be diverse and may affect the establishment of maternal‐fetal tolerance and thereby the outcome of pregnancy. We investigated whether sHLA‐G levels in SP are associated with polymorphisms in the 3′‐untranslated region (UTR) and UTR haplotypes of the HLA‐G gene. Furthermore, we compared the HLA‐G genotype distribution and sHLA‐G levels between men, whose partner experienced unexplained recurrent miscarriage (RM), and controls. Soluble HLA‐G levels (n = 156) and HLA‐G genotyping (n = 176) were determined in SP samples. The concentration of sHLA‐G was significantly associated with several single‐nucleotide polymorphisms (SNPs): the 14 base pair (bp) insertion/deletion (indel), +3010, +3142, +3187, +3196, and + 3509. High levels of sHLA‐G were associated with UTR‐1 and low levels with UTR‐2, UTR‐4, and UTR‐7 (P &lt; .0001). HLA‐G genotype distribution and sHLA‐G levels in SP were not significantly different between the RM group (n = 44) and controls (n = 31). In conclusion, seminal sHLA‐G levels are associated with both singular SNPs and 3UTR haplotypes. HLA‐G genotype and sHLA‐G levels in SP are not different between men whose partner experienced RM and controls, indicating that miscarriages are not solely the result of low sHLA‐G levels in SP. Instead, it is more likely that these miscarriages are the result of a multifactorial immunologic mechanism, whereby the HLA‐G 3′UTR 14 bp ins/ins genotype plays a role in a proportion of the cases. 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We investigated whether sHLA‐G levels in SP are associated with polymorphisms in the 3′‐untranslated region (UTR) and UTR haplotypes of the HLA‐G gene. Furthermore, we compared the HLA‐G genotype distribution and sHLA‐G levels between men, whose partner experienced unexplained recurrent miscarriage (RM), and controls. Soluble HLA‐G levels (n = 156) and HLA‐G genotyping (n = 176) were determined in SP samples. The concentration of sHLA‐G was significantly associated with several single‐nucleotide polymorphisms (SNPs): the 14 base pair (bp) insertion/deletion (indel), +3010, +3142, +3187, +3196, and + 3509. High levels of sHLA‐G were associated with UTR‐1 and low levels with UTR‐2, UTR‐4, and UTR‐7 (P &lt; .0001). HLA‐G genotype distribution and sHLA‐G levels in SP were not significantly different between the RM group (n = 44) and controls (n = 31). In conclusion, seminal sHLA‐G levels are associated with both singular SNPs and 3UTR haplotypes. HLA‐G genotype and sHLA‐G levels in SP are not different between men whose partner experienced RM and controls, indicating that miscarriages are not solely the result of low sHLA‐G levels in SP. Instead, it is more likely that these miscarriages are the result of a multifactorial immunologic mechanism, whereby the HLA‐G 3′UTR 14 bp ins/ins genotype plays a role in a proportion of the cases. Future studies should look into the functions of sHLA‐G in SP and the consequences of low or high levels on the chance to conceive.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>31321883</pmid><doi>10.1111/tan.13628</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-9648-4227</orcidid><orcidid>https://orcid.org/0000-0001-5505-8195</orcidid><oa>free_for_read</oa></addata></record>
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subjects immunology
Original
pregnancy
recurrent miscarriage
seminal plasma
soluble HLA‐G
title Soluble HLA‐G levels in seminal plasma are associated with HLA‐G 3′UTR genotypes and haplotypes
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