A GWAS in Idiopathic/Unexplained Infertile Men Detects a Genomic Region Determining Follicle-Stimulating Hormone Levels
| Autor: | Maria Schubert, Lina Pérez Lanuza, Marius Wöste, Martin Dugas, F David Carmona, Rogelio J Palomino-Morales, Yousif Rassam, Stefanie Heilmann-Heimbach, Frank Tüttelmann, Sabine Kliesch, Jörg Gromoll |
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| Rok vydání: | 2022 |
| Předmět: |
Male
endocrine system single-nucleotide variation (SNV) Endocrinology Diabetes and Metabolism Biochemistry (medical) Clinical Biochemistry Genomics genome-wide association study (GWAS) Biochemistry Polymorphism Single Nucleotide Endocrinology Humans follicle-stimulating hormone (FSH) Follicle Stimulating Hormone Infertility Male idiopathic male infertility Genome-Wide Association Study Retrospective Studies |
| Zdroj: | The Journal of clinical endocrinology and metabolism. 107(8) |
| ISSN: | 1945-7197 |
| Popis: | Context Approximately 70% of infertile men are diagnosed with idiopathic (abnormal semen parameters) or unexplained (normozoospermia) infertility, with the common feature of lacking etiologic factors. Follicle-stimulating hormone (FSH) is essential for initiation and maintenance of spermatogenesis. Certain single-nucleotide variations (SNVs; formerly single-nucleotide polymorphisms [SNPs]) (ie, FSHB c.–211G > T, FSHR c.2039A > G) are associated with FSH, testicular volume, and spermatogenesis. It is unknown to what extent other variants are associated with FSH levels and therewith resemble causative factors for infertility. Objective We aimed to identify further genetic determinants modulating FSH levels in a cohort of men presenting with idiopathic or unexplained infertility. Methods We retrospectively (2010-2018) selected 1900 men with idiopathic/unexplained infertility. In the discovery study (n = 760), a genome-wide association study (GWAS) was performed (Infinium PsychArrays) in association with FSH values (Illumina GenomeStudio, v2.0). Minor allele frequencies (MAFs) were analyzed for the discovery and an independent normozoospermic cohort. In the validation study (n = 1140), TaqMan SNV polymerase chain reaction was conducted for rs11031005 and rs10835638 in association with andrological parameters. Results Imputation revealed 9 SNVs in high linkage disequilibrium, with genome-wide significance (P Conclusions This GWAS delineates the polymorphic FSHB genomic region as the main determinant of FSH levels in men with unexplained or idiopathic infertility. Given the essential role of FSH, molecular detection of one of the identified SNVs that causes lowered FSH and therewith decreases spermatogenesis could resolve the idiopathic/unexplained origin by this etiologic factor. |
| Databáze: | OpenAIRE |
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