FSHB Genotype Identified as a Relevant Diagnostic Parameter Revealed by Cluster Analysis of Men With Idiopathic Infertility
Introduction and ObjectivesAbout 30-75% of infertile men are diagnosed with idiopathic infertility, thereby lacking major causative factors to explain their impaired fertility status. In this study, we used a large cohort of idiopathic infertile men to determine whether subgroups could be identified...
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Frontiers Media S.A.
2021-12-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2021.780403/full |
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| author | Henrike Krenz Andrea Sansone Sabine Kliesch Joerg Gromoll Maria Schubert |
| author_facet | Henrike Krenz Andrea Sansone Sabine Kliesch Joerg Gromoll Maria Schubert |
| author_sort | Henrike Krenz |
| collection | DOAJ |
| description | Introduction and ObjectivesAbout 30-75% of infertile men are diagnosed with idiopathic infertility, thereby lacking major causative factors to explain their impaired fertility status. In this study, we used a large cohort of idiopathic infertile men to determine whether subgroups could be identified by an unbiased clustering approach and whether underlying etiologic factors could be delineated.Patients and MethodsFrom our in-house database Androbase®, we retrospectively selected patients (from 2008 to 2018) with idiopathic male infertility (azoo- to normozoospermia) who fit the following selection criteria: FSH ≥ 1 IU/l, testosterone ≥ 8 nmol/l, ejaculate volume ≥ 1.5 ml. Patients with genetic abnormalities or partners with female factors were excluded.For the identified study population (n=2742), we used common andrologic features (somatic, semen and hormonal parameters, including the FSHB c.-211G>T (rs10835638) single nucleotide polymorphism) for subsequent analyses. Cluster analyses were performed for the entire study population and for two sub-cohorts, which were separated by total sperm count (TSC) thresholds: Cohort A (TSC ≥ 1 mill/ejac; n=2422) and Cohort B (TSC < 1 mill/ejac; n=320). For clustering, the partitioning around medoids method was employed, and the quality was evaluated by average silhouette width.ResultsThe applied cluster approach for the whole study population yielded two separate clusters, which showed significantly different distributions in bi-testicular volume, FSH and FSHB genotype. Cluster 1 contained all men homozygous for G (wildtype) in FSHB c.-211G>T (100%), while Cluster 2 contained most patients carrying a T allele (>96.6%). In the analyses of sub-cohorts A/B, two clusters each were formed too. Again, the strongest segregation markers between the respective clusters were bi-testicular volume, FSH and FSHB c.-211G>T.ConclusionWith this first unbiased approach for revealing putative subgroups within a heterogenous group of idiopathic infertile men, we did indeed identify distinct patient clusters. Surprisingly, across all diverse phenotypes of infertility, the strongest segregation markers were FSHB c.-211G>T, FSH, and bi-testicular volume. Further, Cohorts A and B were significantly separated by FSHB genotype (wildtype vs. T-allele carriers), which supports the notion of a contributing genetic factor. Consequently, FSHB genotyping should be implemented as diagnostic routine in patients with idiopathic infertility. |
| first_indexed | 2024-12-20T16:28:53Z |
| format | Article |
| id | doaj.art-28a63e64489d49fb88a5970dab4387e8 |
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| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-20T16:28:53Z |
| publishDate | 2021-12-01 |
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| series | Frontiers in Endocrinology |
| spelling | doaj.art-28a63e64489d49fb88a5970dab4387e82022-12-21T19:33:18ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922021-12-011210.3389/fendo.2021.780403780403FSHB Genotype Identified as a Relevant Diagnostic Parameter Revealed by Cluster Analysis of Men With Idiopathic InfertilityHenrike Krenz0Andrea Sansone1Sabine Kliesch2Joerg Gromoll3Maria Schubert4 Institute of Medical Informatics, University of Münster, Münster, GermanyDepartment of Systems Medicine, Chair of Endocrinology and Medical Sexology, University of Rome Tor Vergata, Rome, ItalyDepartment of Clinical and Surgical Andrology, Centre of Reproductive Medicine and Andrology (CeRA), University of Münster, Münster, GermanyInstitute of Reproductive and Regenerative Biology, Centre of Reproductive Medicine and Andrology (CeRA), University of Münster, Münster, GermanyDepartment of Clinical and Surgical Andrology, Centre of Reproductive Medicine and Andrology (CeRA), University of Münster, Münster, GermanyIntroduction and ObjectivesAbout 30-75% of infertile men are diagnosed with idiopathic infertility, thereby lacking major causative factors to explain their impaired fertility status. In this study, we used a large cohort of idiopathic infertile men to determine whether subgroups could be identified by an unbiased clustering approach and whether underlying etiologic factors could be delineated.Patients and MethodsFrom our in-house database Androbase®, we retrospectively selected patients (from 2008 to 2018) with idiopathic male infertility (azoo- to normozoospermia) who fit the following selection criteria: FSH ≥ 1 IU/l, testosterone ≥ 8 nmol/l, ejaculate volume ≥ 1.5 ml. Patients with genetic abnormalities or partners with female factors were excluded.For the identified study population (n=2742), we used common andrologic features (somatic, semen and hormonal parameters, including the FSHB c.-211G>T (rs10835638) single nucleotide polymorphism) for subsequent analyses. Cluster analyses were performed for the entire study population and for two sub-cohorts, which were separated by total sperm count (TSC) thresholds: Cohort A (TSC ≥ 1 mill/ejac; n=2422) and Cohort B (TSC < 1 mill/ejac; n=320). For clustering, the partitioning around medoids method was employed, and the quality was evaluated by average silhouette width.ResultsThe applied cluster approach for the whole study population yielded two separate clusters, which showed significantly different distributions in bi-testicular volume, FSH and FSHB genotype. Cluster 1 contained all men homozygous for G (wildtype) in FSHB c.-211G>T (100%), while Cluster 2 contained most patients carrying a T allele (>96.6%). In the analyses of sub-cohorts A/B, two clusters each were formed too. Again, the strongest segregation markers between the respective clusters were bi-testicular volume, FSH and FSHB c.-211G>T.ConclusionWith this first unbiased approach for revealing putative subgroups within a heterogenous group of idiopathic infertile men, we did indeed identify distinct patient clusters. Surprisingly, across all diverse phenotypes of infertility, the strongest segregation markers were FSHB c.-211G>T, FSH, and bi-testicular volume. Further, Cohorts A and B were significantly separated by FSHB genotype (wildtype vs. T-allele carriers), which supports the notion of a contributing genetic factor. Consequently, FSHB genotyping should be implemented as diagnostic routine in patients with idiopathic infertility.https://www.frontiersin.org/articles/10.3389/fendo.2021.780403/fullclusteridiopathic male infertilityFSHB c.-211 G>T polymorphismFSH (follicle stimulating hormone)segregation marker |
| spellingShingle | Henrike Krenz Andrea Sansone Sabine Kliesch Joerg Gromoll Maria Schubert FSHB Genotype Identified as a Relevant Diagnostic Parameter Revealed by Cluster Analysis of Men With Idiopathic Infertility Frontiers in Endocrinology cluster idiopathic male infertility FSHB c.-211 G>T polymorphism FSH (follicle stimulating hormone) segregation marker |
| title | FSHB Genotype Identified as a Relevant Diagnostic Parameter Revealed by Cluster Analysis of Men With Idiopathic Infertility |
| title_full | FSHB Genotype Identified as a Relevant Diagnostic Parameter Revealed by Cluster Analysis of Men With Idiopathic Infertility |
| title_fullStr | FSHB Genotype Identified as a Relevant Diagnostic Parameter Revealed by Cluster Analysis of Men With Idiopathic Infertility |
| title_full_unstemmed | FSHB Genotype Identified as a Relevant Diagnostic Parameter Revealed by Cluster Analysis of Men With Idiopathic Infertility |
| title_short | FSHB Genotype Identified as a Relevant Diagnostic Parameter Revealed by Cluster Analysis of Men With Idiopathic Infertility |
| title_sort | fshb genotype identified as a relevant diagnostic parameter revealed by cluster analysis of men with idiopathic infertility |
| topic | cluster idiopathic male infertility FSHB c.-211 G>T polymorphism FSH (follicle stimulating hormone) segregation marker |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2021.780403/full |
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