Exploring the association of ESR1 and ESR2 gene SNPs with polycystic ovary syndrome in human females: a comprehensive association study
Abstract Background Polycystic Ovary Syndrome (PCOS) affects a significant proportion of human females worldwide and is characterized by hormonal, metabolic, and reproductive dysfunctions, including infertility, irregular menstrual cycles, acanthosis nigricans, and hirsutism. Mutations in the estrog...
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | Journal of Ovarian Research |
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| Online Access: | https://doi.org/10.1186/s13048-023-01335-7 |
| _version_ | 1797273590228320256 |
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| author | Fatima Muccee Naeem Mahmood Ashraf Suhail Razak Tayyaba Afsar Nadia Hussain Fohad Mabood Husain Huma Shafique |
| author_facet | Fatima Muccee Naeem Mahmood Ashraf Suhail Razak Tayyaba Afsar Nadia Hussain Fohad Mabood Husain Huma Shafique |
| author_sort | Fatima Muccee |
| collection | DOAJ |
| description | Abstract Background Polycystic Ovary Syndrome (PCOS) affects a significant proportion of human females worldwide and is characterized by hormonal, metabolic, and reproductive dysfunctions, including infertility, irregular menstrual cycles, acanthosis nigricans, and hirsutism. Mutations in the estrogen receptor genes ESR1 and ESR2, involved in normal follicular development and ovulation, can contribute to development of the PCOS. The present study focuses on investigating the potential correlation between single nucleotide polymorphisms (SNPs) of ESR1 and ESR2 genes and the incidence of this syndrome. Methods For this study, SNPs in ESR1 and ESR2 genes were retrieved from the ENSEMBL database and analyzed for their effect on mutated proteins using different bioinformatics tools including SIFT, PolyPhen, CADD, REVEL, MetaLR, I-Mutant, CELLO2GO, ProtParam, SOPMA, SWISS-MODEL and HDDOCK. Results All the SNPs documented in the present study were deleterious. All the SNPs except rs1583384537, rs1450198518, and rs78255744 decreased protein stability. Two variants rs1463893698 and rs766843910 in the ESR2 gene altered the localization of mutated proteins i.e. in addition to the nucleus, proteins were also found in mitochondria and extracellular, respectively. SNPs rs104893956 in ESR1 and rs140630557, rs140630557, rs1596423459, rs766843910, rs1596405923, rs762454979 and rs1384121511 in ESR2 gene significantly changed the secondary structure of proteins (2D). SNPs that markedly changed 3D configuration included rs1554259481, rs188957694 and rs755667747 in ESR1 gene and rs1463893698, rs140630557, rs1596423459, rs766843910, rs1596405923, rs762454979 and rs1384121511 in ESR2 gene. Variants rs1467954450 (ESR1) and rs140630557 (ESR2) were identified to reduce the binding tendency of ESRα and β receptors with estradiol as reflected by the docking scores i.e. -164.97 and -173.23, respectively. Conclusion Due to the significant impact on the encoded proteins, these variants might be proposed as biomarkers to predict the likelihood of developing PCOS in the future and for diagnostic purposes. |
| first_indexed | 2024-03-07T14:46:34Z |
| format | Article |
| id | doaj.art-4a2e880d29614fc8a80ce6ff2c2781db |
| institution | Directory Open Access Journal |
| issn | 1757-2215 |
| language | English |
| last_indexed | 2024-03-07T14:46:34Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
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| series | Journal of Ovarian Research |
| spelling | doaj.art-4a2e880d29614fc8a80ce6ff2c2781db2024-03-05T19:58:03ZengBMCJournal of Ovarian Research1757-22152024-01-0117111410.1186/s13048-023-01335-7Exploring the association of ESR1 and ESR2 gene SNPs with polycystic ovary syndrome in human females: a comprehensive association studyFatima Muccee0Naeem Mahmood Ashraf1Suhail Razak2Tayyaba Afsar3Nadia Hussain4Fohad Mabood Husain5Huma Shafique6School of Biochemistry and Biotechnology, University of PunjabSchool of Biochemistry and Biotechnology, University of PunjabDepartment of Community Health Sciences, College of Applied Medical Sciences, King Saud UniversityDepartment of Community Health Sciences, College of Applied Medical Sciences, King Saud UniversityDepartment of Pharmaceutical Sciences, College of Pharmacy, Al Ain UniversityDepartment of Food Science and Nutrition, College of Food and Agriculture Sciences, King Saud UniversityInstitute of Cellular Medicine, Newcastle University Medical School, Newcastle University Newcastle Upon TyneAbstract Background Polycystic Ovary Syndrome (PCOS) affects a significant proportion of human females worldwide and is characterized by hormonal, metabolic, and reproductive dysfunctions, including infertility, irregular menstrual cycles, acanthosis nigricans, and hirsutism. Mutations in the estrogen receptor genes ESR1 and ESR2, involved in normal follicular development and ovulation, can contribute to development of the PCOS. The present study focuses on investigating the potential correlation between single nucleotide polymorphisms (SNPs) of ESR1 and ESR2 genes and the incidence of this syndrome. Methods For this study, SNPs in ESR1 and ESR2 genes were retrieved from the ENSEMBL database and analyzed for their effect on mutated proteins using different bioinformatics tools including SIFT, PolyPhen, CADD, REVEL, MetaLR, I-Mutant, CELLO2GO, ProtParam, SOPMA, SWISS-MODEL and HDDOCK. Results All the SNPs documented in the present study were deleterious. All the SNPs except rs1583384537, rs1450198518, and rs78255744 decreased protein stability. Two variants rs1463893698 and rs766843910 in the ESR2 gene altered the localization of mutated proteins i.e. in addition to the nucleus, proteins were also found in mitochondria and extracellular, respectively. SNPs rs104893956 in ESR1 and rs140630557, rs140630557, rs1596423459, rs766843910, rs1596405923, rs762454979 and rs1384121511 in ESR2 gene significantly changed the secondary structure of proteins (2D). SNPs that markedly changed 3D configuration included rs1554259481, rs188957694 and rs755667747 in ESR1 gene and rs1463893698, rs140630557, rs1596423459, rs766843910, rs1596405923, rs762454979 and rs1384121511 in ESR2 gene. Variants rs1467954450 (ESR1) and rs140630557 (ESR2) were identified to reduce the binding tendency of ESRα and β receptors with estradiol as reflected by the docking scores i.e. -164.97 and -173.23, respectively. Conclusion Due to the significant impact on the encoded proteins, these variants might be proposed as biomarkers to predict the likelihood of developing PCOS in the future and for diagnostic purposes.https://doi.org/10.1186/s13048-023-01335-7Polycystic ovary syndromeSingle nucleotide polymorphismsCoding sequenceSub-cellular localizationSecondary structure |
| spellingShingle | Fatima Muccee Naeem Mahmood Ashraf Suhail Razak Tayyaba Afsar Nadia Hussain Fohad Mabood Husain Huma Shafique Exploring the association of ESR1 and ESR2 gene SNPs with polycystic ovary syndrome in human females: a comprehensive association study Journal of Ovarian Research Polycystic ovary syndrome Single nucleotide polymorphisms Coding sequence Sub-cellular localization Secondary structure |
| title | Exploring the association of ESR1 and ESR2 gene SNPs with polycystic ovary syndrome in human females: a comprehensive association study |
| title_full | Exploring the association of ESR1 and ESR2 gene SNPs with polycystic ovary syndrome in human females: a comprehensive association study |
| title_fullStr | Exploring the association of ESR1 and ESR2 gene SNPs with polycystic ovary syndrome in human females: a comprehensive association study |
| title_full_unstemmed | Exploring the association of ESR1 and ESR2 gene SNPs with polycystic ovary syndrome in human females: a comprehensive association study |
| title_short | Exploring the association of ESR1 and ESR2 gene SNPs with polycystic ovary syndrome in human females: a comprehensive association study |
| title_sort | exploring the association of esr1 and esr2 gene snps with polycystic ovary syndrome in human females a comprehensive association study |
| topic | Polycystic ovary syndrome Single nucleotide polymorphisms Coding sequence Sub-cellular localization Secondary structure |
| url | https://doi.org/10.1186/s13048-023-01335-7 |
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