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

(Pages: 450-456)
Zahra Chekini, M.Sc, 1,2Maryam Shahhoseini, Ph.D, 3,4Reza Aflatoonian, M.D., Ph.D., 2,*Parvaneh Afsharian, Ph.D, 4,*
Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
*Corresponding Addresses: P.O.Box: 16635-148 Department of Endocrinology and Female Infertility Reproductive Biomedicine Research Center Royan Institute for Reproductive Biomedicine ACECR Tehran Iran P.O.Box: 16635-148 Department of Genetics Reproductive Biomedicine Research Center Royan Institute for Reproductive Biomedicine ACECR Tehran Iran Emails:r.aflatoonian@gmail.com,pafshar@royaninstitute.org
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Chekini Zahra, Shahhoseini Maryam, Aflatoonian Reza, Afsharian Parvaneh. The Relationship between Functional Promoter Variants of Macrophage Migration Inhibitory Factor and Endometriosis. Cell J. 2021; 22(4): 450-456.

Abstract

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 CATT7 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 CATT5/G in controls [global P value=0.044]. Additionally, the CATT5/C and CATT7/G haplotypes were not detected in any groups. Expression level of mRNA in ectopic tissue of endometriosis patients with CATT6,7/CC haplotype, were significantly higher compared to other haplotypes including CATT5,5/GG (2.91 fold, P=0.007), CATT5,5/GC (2.48 fold, P=0.047) and CATT6,6/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 CATT6/C and CATT7/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.