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Sadat Eshaghi, F., Dehghan Tezerjani, M., Ghasemi, N., & Dehghani, M. (2022). Association study of ESR1 rs9340799, rs2234693, and MMP2 rs243865 variants in Iranian women with premature ovarian insufficiency: A case-control study. International Journal of Reproductive BioMedicine (IJRM), 20(10), 841–850. https://doi.org/10.18502/ijrm.v20i10.12268
https://doi.org/10.18502/ijrm.v20i10.12268
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Farzaneh Sadat Eshaghi
Farzaneh Sadat Eshaghi
Department of Genetics, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
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Masoud Dehghan Tezerjani
Masoud Dehghan Tezerjani
Abortion Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
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Nasrin Ghasemi
Nasrin Ghasemi
Abortion Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
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Mohammadreza Dehghani
Mohammadreza Dehghani
Medical Genetics Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Published Date
- Nov 2, 2022
Association study of ESR1 rs9340799, rs2234693, and MMP2 rs243865 variants in Iranian women with premature ovarian insufficiency: A case-control study
Abstract
Background: Primary ovarian insufficiency (POI) is a rare disease clinically characterized by ovarian follicles depletion or dysfunction and menopause before the age of 40 yr as the cut-off age for POI. It is a complex disease, and its etiology involves several factors. However, genetic factors have a predominant role in the susceptibility to the disease.
Objective: This study aims to investigate the polymorphisms of rs243865 in the matrix metallopeptidase 2 (MMP2) gene and rs2234693 and rs9340799 in the estrogen receptor 1 (ESR1) gene with susceptibility to POI in Iranian women under 35 yr.
Materials and Methods: This case-control study was performed on 150 women with POI and 150 healthy women who were referred to Yazd Reproductive Sciences Institute, Yazd, Iran between May-October 2020. The genotyping of ESR1 rs9340799, rs2234693, and MMP2 rs243865 polymorphism was done using tetra-amplification refractory mutation system-polymerase chain reaction. In addition, haplotype analysis and linkage disequilibrium were investigated by SNPanalyzer software.
Results: Our study revealed the frequency of rs243865 TT, CC genotypes in the MMP2 gene and rs2234693 CC, TT; and rs9340799 GG, AA in the ESR1 gene were more prevalent in the case group compared to the control group. In addition, ESR1 rs2234693 and rs9340799 genotypes showed significant association with the development of the disease in our population. Among 4 haplotypes for 2 polymorphisms in the ESR1 gene, rs2234693T/rs9340799A haplotype was associated with conferring risk to POI.
Conclusion: ESR1 rs2234693 and rs9340799 polymorphism were strongly associated with our population’s POI.
Key words: Matrix metalloproteinase-2, Estrogen receptor alpha, Primary ovarian insufficiency, Female infertility.
References
[1] Chen Q, Ke H, Luo X, Wang L, Wu Y, Tang S, et al. Rare deleterious BUB1B variants induce premature ovarian insufficiency and early menopause. Hum Mol Genet 2020; 29: 2698–2707.
[2] Fattet A-J, Toupance S, Thornton SN, Monnin N, Gueant J-L, Benetos A, et al. Telomere length in granulosa cells and leukocytes: A potential marker of female fertility? A systematic review of the literature. J Ovarian Res 2020; 13: 96.
[3] Rossetti R, Ferrari I, Bonomi M, Persani L. Genetics of primary ovarian insufficiency. Clin Genet 2017; 91: 183–198.
[4] Sharif K, Watad A, Bridgewood Ch, Kanduc D, Amital H, Shoenfeld Y. Insights into the autoimmune aspect of premature ovarian insufficiency. Best Pract Res Clin Endocrinol Metab 2019; 33: 101323.
[5] Wolak D, Sechman A, Hrabia A. Effect of eCG treatment on gene expression of selected matrix metalloproteinases (MMP-2, MMP-7, MMP-9, MMP-10, and MMP-13) and the tissue inhibitors of metalloproteinases (TIMP-2 and TIMP- 3) in the chicken ovary. Anim Reprod Sci 2021; 224: 106666.
[6] An HJ, Ahn EH, Kim JO, Park HS, Ryu ChS, Cho SH, et al. Association between tissue inhibitor of metalloproteinase (TIMP) genetic polymorphisms and primary ovarian insufficiency (POI). Maturitas 2019; 120: 77–82.
[7] Kim YR, Jeon YJ, Kim HS, Kim JO, Moon MJ, Ahn EH, et al. Association study of five functional polymorphisms in matrix metalloproteinase-2, -3, and -9 genes with risk of primary ovarian insufficiency in Korean women. Maturitas 2015; 80: 192–197.
[8] Asadzadeh R, Khosravi Sh, Zavareh S, Ghorbanian MT, Paylakhi SH, Mohebbi SR. Vitrification affects the expression of matrix metalloproteinases and their tissue inhibitors of mouse ovarian tissue. Int J Reprod Med 2016; 14: 173–180.
[9] Li J, Dalgleish R, Vujovic S, Dragojevic-Dikic S, Ivanisevic M, Ivovic M, et al. Microsatellite variation of ESR1, ESR2, and AR in Serbian women with primary ovarian insufficiency. Climacteric 2018; 21: 472–477.
[10] Akande RO, Ibrahim Y. Genetics of primary ovarian insufficiency. Clin Obstet Gynecol 2020; 63: 687–705.
[11] Qin Y, Sun M, You L, Wei D, Sun J, Liang X, et al. ESR1, HK3 and BRSK1 gene variants are associated with both age at natural menopause and premature ovarian failure. Orphanet J Rare Dis 2012; 7: 5.
[12] Cordts EB, Santos AA, Peluso C, Bianco B, Barbosa CP, Christofolini DM. Risk of premature ovarian failure is associated to the PvuII polymorphism at estrogen receptor gene ESR1. J Assist Reprod Genet 2012; 29: 1421–1425.
[13] M’Rabet N, Moffat R, Helbling S, Kaech A, Zhang H, de Geyter C. The CC-allele of the PvuII polymorphic variant in intron 1 of the α-estrogen receptor gene is significantly more prevalent among infertile women at risk of premature ovarian aging. Fertil Steril 2012; 98: 965–972.
[14] Vichinsartvichai P. Primary ovarian insufficiency associated with autosomal abnormalities: From chromosome to genome-wide and beyond. Menopause 2016; 23: 806–815.
[15] Mahmoudi Sh, Badali H, Rezaie S, Azarnezhad A, Barac A, Kord M, et al. A simple and low cost tetra-primer ARMSPCR method for detection triazole-resistant Aspergillus fumigatus. Mol Biol Rep 2019; 46: 4537–4543.
[16] Linjawi S, Al-Gaithy Z, Sindi S, Hamdi N, Linjawi A, Alrofidi A. Tetra-primer ARMS PCR as an efficient alternative for SNPs detection in molecular diagnostic: A comparison study. Eur J Pharm Med Res 2019; 6: 91–96.
[17] Greene AD, Patounakis G, Segars JH. Genetic associations with diminished ovarian reserve: A systematic review of the literature. J Assist Reprod Genet 2014; 31: 935–946.
[18] He M, Shu J, Huang X, Tang H. Association between estrogen receptora gene (ESR1) PvuII (T/C) and XbaI (A/G) polymorphisms and premature ovarian failure risk: Evidence from a meta-analysis. J Assist Reprod Genet 2015; 32: 297–304.
[19] Sapkota Y, Steinthorsdottir V, Morris AP, Fassbender A, Rahmioglu N, De Vivo I, et al. Meta-analysis identifies five novel loci associated with endometriosis highlighting key genes involved in hormone metabolism. Nat Commun 2017; 8: 15539.
[20] Gallagher CS, Mäkinen N, Harris HR, Rahmioglu N, Uimari O, Cook JP, et al. Genome-wide association and epidemiological analyses reveal common genetic origins between uterine leiomyomata and endometriosis. Nat Commun 2019; 10: 4857.
[21] Michailidou K, Lindstrom S, Dennis J, Beesley J, Hui Sh, Kar S, et al. Association analysis identifies 65 new breast cancer risk loci. Nature 2017; 551: 92–94.
[22] Liu L, Tan R, Cui Y, Liu J, Wu J. Estrogen receptor α gene (ESR1) polymorphisms associated with idiopathic premature ovarian failure in Chinese women. Gynecol Endocrinol 2013; 29: 182–185.
[23] Venturella R, De Vivo V, Carlea A, D’Alessandro P, Saccone G, Arduino B, et al. The genetics of non-syndromic primary ovarian insufficiency: A systematic review. Int J Fertil Steril 2019; 13: 161–168.
[24] Li J, Vujovic S, Dalgleish R, Thompson J, Dragojevic-Dikic S, Al-Azzawi F. Lack of association between ESR1 gene polymorphisms and premature ovarian failure in Serbian women. Climacteric 2014; 17: 247–251.
[25] Anousha N, Hossein-Nezhad A, Biramijamal F, Rahmani A, Maghbooli Z, Aghababaei E, et al. Association study of estrogen receptor alpha gene polymorphisms with spontaneous abortion: Is this a possible reason for unexplained spontaneous abortion? BioMed Res Inter 2013; 2013: 256470.
[26] Pu D, Xing Y, Gao Y, Gu L, Wu J. Gene variation and premature ovarian failure: A meta-analysis. Eur J Obstet Gynecol Reprod Biol 2014; 182: 226–237.
[27] Sindiani AM, Batiha O, Esra’a Al-zoubi SK, Alsoukhni G, Alkofahi A, Alahmad NA, et al. Association of singlenucleotide polymorphisms in the ESR2 and FSHR genes with poor ovarian response in infertile Jordanian women. Clin Exp Reprod Med 2021; 48: 69–79.
[28] Fernandez R, Delgado-Zayas E, Ramirez K, Cortes- Cortes J, Gomez-Gil E, Esteva I, et al. Analysis of four polymorphisms located at the promoter of the estrogen receptor alpha ESR1 gene in a population with gender incongruence. Sex Med 2020; 8: 490–500.
[29] Kasai M, Ishida R, Nakahara K, Okumura K, Aoki K. Mesenchymal cell differentiation and diseases: Involvement of translin/TRAX complexes and associated proteins. Ann N Y Acad Sci 2018; 1421: 37–45.
[30] Li H, Blanco MA. A catalytic dependent role for DNMT3B in tumor suppression. EBioMedicine 2021; 65: 103237.
[31] Habel AF, Ghali RM, Bouaziz H, Daldoul A, Hadj-Ahmed M, Mokrani A, et al. Common matrix metalloproteinase-2 gene variants and altered susceptibility to breast cancer and associated features in Tunisian women. Tumor Biol 2019; 41: 1010428319845749.
[2] Fattet A-J, Toupance S, Thornton SN, Monnin N, Gueant J-L, Benetos A, et al. Telomere length in granulosa cells and leukocytes: A potential marker of female fertility? A systematic review of the literature. J Ovarian Res 2020; 13: 96.
[3] Rossetti R, Ferrari I, Bonomi M, Persani L. Genetics of primary ovarian insufficiency. Clin Genet 2017; 91: 183–198.
[4] Sharif K, Watad A, Bridgewood Ch, Kanduc D, Amital H, Shoenfeld Y. Insights into the autoimmune aspect of premature ovarian insufficiency. Best Pract Res Clin Endocrinol Metab 2019; 33: 101323.
[5] Wolak D, Sechman A, Hrabia A. Effect of eCG treatment on gene expression of selected matrix metalloproteinases (MMP-2, MMP-7, MMP-9, MMP-10, and MMP-13) and the tissue inhibitors of metalloproteinases (TIMP-2 and TIMP- 3) in the chicken ovary. Anim Reprod Sci 2021; 224: 106666.
[6] An HJ, Ahn EH, Kim JO, Park HS, Ryu ChS, Cho SH, et al. Association between tissue inhibitor of metalloproteinase (TIMP) genetic polymorphisms and primary ovarian insufficiency (POI). Maturitas 2019; 120: 77–82.
[7] Kim YR, Jeon YJ, Kim HS, Kim JO, Moon MJ, Ahn EH, et al. Association study of five functional polymorphisms in matrix metalloproteinase-2, -3, and -9 genes with risk of primary ovarian insufficiency in Korean women. Maturitas 2015; 80: 192–197.
[8] Asadzadeh R, Khosravi Sh, Zavareh S, Ghorbanian MT, Paylakhi SH, Mohebbi SR. Vitrification affects the expression of matrix metalloproteinases and their tissue inhibitors of mouse ovarian tissue. Int J Reprod Med 2016; 14: 173–180.
[9] Li J, Dalgleish R, Vujovic S, Dragojevic-Dikic S, Ivanisevic M, Ivovic M, et al. Microsatellite variation of ESR1, ESR2, and AR in Serbian women with primary ovarian insufficiency. Climacteric 2018; 21: 472–477.
[10] Akande RO, Ibrahim Y. Genetics of primary ovarian insufficiency. Clin Obstet Gynecol 2020; 63: 687–705.
[11] Qin Y, Sun M, You L, Wei D, Sun J, Liang X, et al. ESR1, HK3 and BRSK1 gene variants are associated with both age at natural menopause and premature ovarian failure. Orphanet J Rare Dis 2012; 7: 5.
[12] Cordts EB, Santos AA, Peluso C, Bianco B, Barbosa CP, Christofolini DM. Risk of premature ovarian failure is associated to the PvuII polymorphism at estrogen receptor gene ESR1. J Assist Reprod Genet 2012; 29: 1421–1425.
[13] M’Rabet N, Moffat R, Helbling S, Kaech A, Zhang H, de Geyter C. The CC-allele of the PvuII polymorphic variant in intron 1 of the α-estrogen receptor gene is significantly more prevalent among infertile women at risk of premature ovarian aging. Fertil Steril 2012; 98: 965–972.
[14] Vichinsartvichai P. Primary ovarian insufficiency associated with autosomal abnormalities: From chromosome to genome-wide and beyond. Menopause 2016; 23: 806–815.
[15] Mahmoudi Sh, Badali H, Rezaie S, Azarnezhad A, Barac A, Kord M, et al. A simple and low cost tetra-primer ARMSPCR method for detection triazole-resistant Aspergillus fumigatus. Mol Biol Rep 2019; 46: 4537–4543.
[16] Linjawi S, Al-Gaithy Z, Sindi S, Hamdi N, Linjawi A, Alrofidi A. Tetra-primer ARMS PCR as an efficient alternative for SNPs detection in molecular diagnostic: A comparison study. Eur J Pharm Med Res 2019; 6: 91–96.
[17] Greene AD, Patounakis G, Segars JH. Genetic associations with diminished ovarian reserve: A systematic review of the literature. J Assist Reprod Genet 2014; 31: 935–946.
[18] He M, Shu J, Huang X, Tang H. Association between estrogen receptora gene (ESR1) PvuII (T/C) and XbaI (A/G) polymorphisms and premature ovarian failure risk: Evidence from a meta-analysis. J Assist Reprod Genet 2015; 32: 297–304.
[19] Sapkota Y, Steinthorsdottir V, Morris AP, Fassbender A, Rahmioglu N, De Vivo I, et al. Meta-analysis identifies five novel loci associated with endometriosis highlighting key genes involved in hormone metabolism. Nat Commun 2017; 8: 15539.
[20] Gallagher CS, Mäkinen N, Harris HR, Rahmioglu N, Uimari O, Cook JP, et al. Genome-wide association and epidemiological analyses reveal common genetic origins between uterine leiomyomata and endometriosis. Nat Commun 2019; 10: 4857.
[21] Michailidou K, Lindstrom S, Dennis J, Beesley J, Hui Sh, Kar S, et al. Association analysis identifies 65 new breast cancer risk loci. Nature 2017; 551: 92–94.
[22] Liu L, Tan R, Cui Y, Liu J, Wu J. Estrogen receptor α gene (ESR1) polymorphisms associated with idiopathic premature ovarian failure in Chinese women. Gynecol Endocrinol 2013; 29: 182–185.
[23] Venturella R, De Vivo V, Carlea A, D’Alessandro P, Saccone G, Arduino B, et al. The genetics of non-syndromic primary ovarian insufficiency: A systematic review. Int J Fertil Steril 2019; 13: 161–168.
[24] Li J, Vujovic S, Dalgleish R, Thompson J, Dragojevic-Dikic S, Al-Azzawi F. Lack of association between ESR1 gene polymorphisms and premature ovarian failure in Serbian women. Climacteric 2014; 17: 247–251.
[25] Anousha N, Hossein-Nezhad A, Biramijamal F, Rahmani A, Maghbooli Z, Aghababaei E, et al. Association study of estrogen receptor alpha gene polymorphisms with spontaneous abortion: Is this a possible reason for unexplained spontaneous abortion? BioMed Res Inter 2013; 2013: 256470.
[26] Pu D, Xing Y, Gao Y, Gu L, Wu J. Gene variation and premature ovarian failure: A meta-analysis. Eur J Obstet Gynecol Reprod Biol 2014; 182: 226–237.
[27] Sindiani AM, Batiha O, Esra’a Al-zoubi SK, Alsoukhni G, Alkofahi A, Alahmad NA, et al. Association of singlenucleotide polymorphisms in the ESR2 and FSHR genes with poor ovarian response in infertile Jordanian women. Clin Exp Reprod Med 2021; 48: 69–79.
[28] Fernandez R, Delgado-Zayas E, Ramirez K, Cortes- Cortes J, Gomez-Gil E, Esteva I, et al. Analysis of four polymorphisms located at the promoter of the estrogen receptor alpha ESR1 gene in a population with gender incongruence. Sex Med 2020; 8: 490–500.
[29] Kasai M, Ishida R, Nakahara K, Okumura K, Aoki K. Mesenchymal cell differentiation and diseases: Involvement of translin/TRAX complexes and associated proteins. Ann N Y Acad Sci 2018; 1421: 37–45.
[30] Li H, Blanco MA. A catalytic dependent role for DNMT3B in tumor suppression. EBioMedicine 2021; 65: 103237.
[31] Habel AF, Ghali RM, Bouaziz H, Daldoul A, Hadj-Ahmed M, Mokrani A, et al. Common matrix metalloproteinase-2 gene variants and altered susceptibility to breast cancer and associated features in Tunisian women. Tumor Biol 2019; 41: 1010428319845749.