Cargando…

The Relationship between Functional Promoter Variants of Macrophage Migration Inhibitory Factor and Endometriosis

OBJECTIVE: Endometriosis is a common gynecological and inflammatory disorder. Macrophage migration inhibitory factor (MIF) is a key pro-inflammatory cytokine that is secreted by accumulated active macrophages in ectopic endometrial tissues. Two promoter polymorphisms of MIF [-794(CATT)(5–8)/-173G/C]...

Descripción completa

Detalles Bibliográficos
Autores principales: Chekini, Zahra, Shahhoseini, Maryam, Aflatoonian, Reza, Afsharian, Parvaneh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Royan Institute 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211282/
https://www.ncbi.nlm.nih.gov/pubmed/32347038
http://dx.doi.org/10.22074/cellj.2021.6858
_version_ 1783531424034324480
author Chekini, Zahra
Shahhoseini, Maryam
Aflatoonian, Reza
Afsharian, Parvaneh
author_facet Chekini, Zahra
Shahhoseini, Maryam
Aflatoonian, Reza
Afsharian, Parvaneh
author_sort Chekini, Zahra
collection PubMed
description OBJECTIVE: Endometriosis is a common gynecological and inflammatory disorder. Macrophage migration inhibitory factor (MIF) is a key pro-inflammatory cytokine that is secreted by accumulated active macrophages in ectopic endometrial tissues. Two promoter polymorphisms of MIF [-794(CATT)(5–8)/-173G/C] were identified to susceptibility and severity of several immune and inflammatory diseases. We aimed to evaluate the possible association between MIF promoter polymorphisms and susceptibly to endometriosis and its corolation with mRNA level. MATERIALS AND METHODS: This case-control study was performed in Royan Institute from 2015 to 2017. Polymorphisms were evaluated in 106 endometriosis patients and 110 controls. For 17 endometrioma tissues, gene expression studies were conducted during secretory phase of menstrual cycle. Restriction fragment length polymorphism (RFLP) analysis was performed to determine -173G/C polymorphism and -794(CATT)(5–8) were detected by sequencing. Quantitative polymerase chain reaction (Q-PCR) was carried out to determine MIF expression level. RESULTS: Homozygote of CATT(7) was observed only in endometriosis whilst we did not detect the significant allele and genotype variation in both groups. The homozygotes for -794(CATT)(5–8) and -173G/C polymorphisms were obtained to estimate the haplotype frequencies. Significantly higher haplotype frequencies were observed for CATT(5)/G in controls [global P value=0.044]. Additionally, the CATT(5)/C and CATT(7)/G haplotypes were not detected in any groups. Expression level of mRNA in ectopic tissue of endometriosis patients with CATT(6,7)/CC haplotype, were significantly higher compared to other haplotypes including CATT(5,5)/GG (2.91 fold, P=0.007), CATT(5,5)/GC (2.48 fold, P=0.047) and CATT(6,6)/GG (2.08 fold, P=0.046). CONCLUSION: We report, for the first time, a strong linkage between the decreased repetition of CATT and G allele in control and CATT(6)/C and CATT(7)/C haplotypes in endometriosis patients. Increased MIF expression is affected by genetic variants in the MIF promoter in ectopic endometrial tissues. This promoter haplotype might play an important role in the development and establishment of endometriosis.
format Online
Article
Text
id pubmed-7211282
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Royan Institute
record_format MEDLINE/PubMed
spelling pubmed-72112822021-01-01 The Relationship between Functional Promoter Variants of Macrophage Migration Inhibitory Factor and Endometriosis Chekini, Zahra Shahhoseini, Maryam Aflatoonian, Reza Afsharian, Parvaneh Cell J Original Article OBJECTIVE: Endometriosis is a common gynecological and inflammatory disorder. Macrophage migration inhibitory factor (MIF) is a key pro-inflammatory cytokine that is secreted by accumulated active macrophages in ectopic endometrial tissues. Two promoter polymorphisms of MIF [-794(CATT)(5–8)/-173G/C] were identified to susceptibility and severity of several immune and inflammatory diseases. We aimed to evaluate the possible association between MIF promoter polymorphisms and susceptibly to endometriosis and its corolation with mRNA level. MATERIALS AND METHODS: This case-control study was performed in Royan Institute from 2015 to 2017. Polymorphisms were evaluated in 106 endometriosis patients and 110 controls. For 17 endometrioma tissues, gene expression studies were conducted during secretory phase of menstrual cycle. Restriction fragment length polymorphism (RFLP) analysis was performed to determine -173G/C polymorphism and -794(CATT)(5–8) were detected by sequencing. Quantitative polymerase chain reaction (Q-PCR) was carried out to determine MIF expression level. RESULTS: Homozygote of CATT(7) was observed only in endometriosis whilst we did not detect the significant allele and genotype variation in both groups. The homozygotes for -794(CATT)(5–8) and -173G/C polymorphisms were obtained to estimate the haplotype frequencies. Significantly higher haplotype frequencies were observed for CATT(5)/G in controls [global P value=0.044]. Additionally, the CATT(5)/C and CATT(7)/G haplotypes were not detected in any groups. Expression level of mRNA in ectopic tissue of endometriosis patients with CATT(6,7)/CC haplotype, were significantly higher compared to other haplotypes including CATT(5,5)/GG (2.91 fold, P=0.007), CATT(5,5)/GC (2.48 fold, P=0.047) and CATT(6,6)/GG (2.08 fold, P=0.046). CONCLUSION: We report, for the first time, a strong linkage between the decreased repetition of CATT and G allele in control and CATT(6)/C and CATT(7)/C haplotypes in endometriosis patients. Increased MIF expression is affected by genetic variants in the MIF promoter in ectopic endometrial tissues. This promoter haplotype might play an important role in the development and establishment of endometriosis. Royan Institute 2021 2020-04-22 /pmc/articles/PMC7211282/ /pubmed/32347038 http://dx.doi.org/10.22074/cellj.2021.6858 Text en Any use, distribution, reproduction or abstract of this publication in any medium, with the exception of commercial purposes, is permitted provided the original work is properly cited. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Chekini, Zahra
Shahhoseini, Maryam
Aflatoonian, Reza
Afsharian, Parvaneh
The Relationship between Functional Promoter Variants of Macrophage Migration Inhibitory Factor and Endometriosis
title The Relationship between Functional Promoter Variants of Macrophage Migration Inhibitory Factor and Endometriosis
title_full The Relationship between Functional Promoter Variants of Macrophage Migration Inhibitory Factor and Endometriosis
title_fullStr The Relationship between Functional Promoter Variants of Macrophage Migration Inhibitory Factor and Endometriosis
title_full_unstemmed The Relationship between Functional Promoter Variants of Macrophage Migration Inhibitory Factor and Endometriosis
title_short The Relationship between Functional Promoter Variants of Macrophage Migration Inhibitory Factor and Endometriosis
title_sort relationship between functional promoter variants of macrophage migration inhibitory factor and endometriosis
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211282/
https://www.ncbi.nlm.nih.gov/pubmed/32347038
http://dx.doi.org/10.22074/cellj.2021.6858
work_keys_str_mv AT chekinizahra therelationshipbetweenfunctionalpromotervariantsofmacrophagemigrationinhibitoryfactorandendometriosis
AT shahhoseinimaryam therelationshipbetweenfunctionalpromotervariantsofmacrophagemigrationinhibitoryfactorandendometriosis
AT aflatoonianreza therelationshipbetweenfunctionalpromotervariantsofmacrophagemigrationinhibitoryfactorandendometriosis
AT afsharianparvaneh therelationshipbetweenfunctionalpromotervariantsofmacrophagemigrationinhibitoryfactorandendometriosis
AT chekinizahra relationshipbetweenfunctionalpromotervariantsofmacrophagemigrationinhibitoryfactorandendometriosis
AT shahhoseinimaryam relationshipbetweenfunctionalpromotervariantsofmacrophagemigrationinhibitoryfactorandendometriosis
AT aflatoonianreza relationshipbetweenfunctionalpromotervariantsofmacrophagemigrationinhibitoryfactorandendometriosis
AT afsharianparvaneh relationshipbetweenfunctionalpromotervariantsofmacrophagemigrationinhibitoryfactorandendometriosis