Whole Exome Sequencing Reveals Rare Variants in Genes Associated with Metabolic Disorders in Women with PCOS
Background: Polycystic ovary syndrome (PCOS) is a complex genetic trait, the pathogenesis of which is governed by an interplay of genetic and epigenetic factors. However, the aetiology of PCOS is not fully understood. Aims: The objective of this study was to investigate the genetic causes of PCOS by...
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2023-10-01
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| Series: | Journal of Human Reproductive Sciences |
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| Online Access: | https://journals.lww.com/10.4103/jhrs.jhrs_13_23 |
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| author | Priyal Sharma Ashutosh Halder Manish Jain Manish Tripathi |
| author_facet | Priyal Sharma Ashutosh Halder Manish Jain Manish Tripathi |
| author_sort | Priyal Sharma |
| collection | DOAJ |
| description | Background:
Polycystic ovary syndrome (PCOS) is a complex genetic trait, the pathogenesis of which is governed by an interplay of genetic and epigenetic factors. However, the aetiology of PCOS is not fully understood.
Aims:
The objective of this study was to investigate the genetic causes of PCOS by identifying rare variants in genes implicated in its pathophysiology.
Settings and Design:
This was a hospital-based observational study.
Materials and Methods:
We used whole-exome sequencing for 52 PCOS women to identify the rare variants in genes related to PCOS pathogenesis. Subsequently, we analysed these variants using in silico prediction software to determine their functional effects. We then assessed the relationship between these variants and the clinical outcomes of the patients.
Statistical Analysis Used:
Student’s t-test and Fisher’s exact test were used to compare clinical parameters and frequency differences amongst PCOS patients with and without variants.
Results:
A total of four rare exonic variants in obesity- and hyperinsulinaemia-related genes including UCP1 (p.Thr227Ile), UCP2 (p.Arg88Cys), IRS1 (p.Ser892Gly) and GHRL (p.Leu72Met) were identified in eight patients. Significant differences were observed between the patients carrying variants and those without variants. PCOS patients with identified variants exhibited significantly higher average body mass index and fasting insulin levels of PCOS subjects with identified variants compared to those without variants (P < 0.05). Additionally, there were significant differences in the variant frequencies of four variants when compared to the population database (P < 0.05).
Conclusion:
This study shows a prevalence of rare variants in obesity and hyperinsulinaemia-related genes in a cohort of PCOS women, thereby underscoring the impact of the identified rare variants on the development of obesity and associated metabolic derangements in PCOS women. |
| format | Article |
| id | doaj-art-3f2db3e010a5455a8a4c0c21fba7cc4d |
| institution | Kabale University |
| issn | 0974-1208 1998-4766 |
| language | English |
| publishDate | 2023-10-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Journal of Human Reproductive Sciences |
| spelling | doaj-art-3f2db3e010a5455a8a4c0c21fba7cc4d2025-02-10T09:11:37ZengWolters Kluwer Medknow PublicationsJournal of Human Reproductive Sciences0974-12081998-47662023-10-0116430731610.4103/jhrs.jhrs_13_23Whole Exome Sequencing Reveals Rare Variants in Genes Associated with Metabolic Disorders in Women with PCOSPriyal SharmaAshutosh HalderManish JainManish TripathiBackground: Polycystic ovary syndrome (PCOS) is a complex genetic trait, the pathogenesis of which is governed by an interplay of genetic and epigenetic factors. However, the aetiology of PCOS is not fully understood. Aims: The objective of this study was to investigate the genetic causes of PCOS by identifying rare variants in genes implicated in its pathophysiology. Settings and Design: This was a hospital-based observational study. Materials and Methods: We used whole-exome sequencing for 52 PCOS women to identify the rare variants in genes related to PCOS pathogenesis. Subsequently, we analysed these variants using in silico prediction software to determine their functional effects. We then assessed the relationship between these variants and the clinical outcomes of the patients. Statistical Analysis Used: Student’s t-test and Fisher’s exact test were used to compare clinical parameters and frequency differences amongst PCOS patients with and without variants. Results: A total of four rare exonic variants in obesity- and hyperinsulinaemia-related genes including UCP1 (p.Thr227Ile), UCP2 (p.Arg88Cys), IRS1 (p.Ser892Gly) and GHRL (p.Leu72Met) were identified in eight patients. Significant differences were observed between the patients carrying variants and those without variants. PCOS patients with identified variants exhibited significantly higher average body mass index and fasting insulin levels of PCOS subjects with identified variants compared to those without variants (P < 0.05). Additionally, there were significant differences in the variant frequencies of four variants when compared to the population database (P < 0.05). Conclusion: This study shows a prevalence of rare variants in obesity and hyperinsulinaemia-related genes in a cohort of PCOS women, thereby underscoring the impact of the identified rare variants on the development of obesity and associated metabolic derangements in PCOS women.https://journals.lww.com/10.4103/jhrs.jhrs_13_23hyperinsulinaemiaobesitypolycystic ovary syndromerare variantswhole-exome sequencing |
| spellingShingle | Priyal Sharma Ashutosh Halder Manish Jain Manish Tripathi Whole Exome Sequencing Reveals Rare Variants in Genes Associated with Metabolic Disorders in Women with PCOS Journal of Human Reproductive Sciences hyperinsulinaemia obesity polycystic ovary syndrome rare variants whole-exome sequencing |
| title | Whole Exome Sequencing Reveals Rare Variants in Genes Associated with Metabolic Disorders in Women with PCOS |
| title_full | Whole Exome Sequencing Reveals Rare Variants in Genes Associated with Metabolic Disorders in Women with PCOS |
| title_fullStr | Whole Exome Sequencing Reveals Rare Variants in Genes Associated with Metabolic Disorders in Women with PCOS |
| title_full_unstemmed | Whole Exome Sequencing Reveals Rare Variants in Genes Associated with Metabolic Disorders in Women with PCOS |
| title_short | Whole Exome Sequencing Reveals Rare Variants in Genes Associated with Metabolic Disorders in Women with PCOS |
| title_sort | whole exome sequencing reveals rare variants in genes associated with metabolic disorders in women with pcos |
| topic | hyperinsulinaemia obesity polycystic ovary syndrome rare variants whole-exome sequencing |
| url | https://journals.lww.com/10.4103/jhrs.jhrs_13_23 |
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