Polymorphism in the Alternative Donor Site of the Cryptic Exon of LHCGR: Functional Consequences and Associations with Testosterone Level
| Autor: | Ying Yang, Bing Han, Jie Qiao, Wei Liu, Yanping Kuang, Jiajun Wu, Shuang-Xia Zhao, Hui Zhu, Jiqiang Si, Wenjiao Zhu, Qifeng Lyu, Wei-Ran Chai, Huai-Dong Song, Tong Cheng, Mengxia Fan |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine endocrine system Genotype Biology Polymorphism Single Nucleotide Article Male infertility 03 medical and health sciences 0302 clinical medicine Gene Frequency Odds Ratio medicine Humans SNP Testosterone Gene Infertility Male Azoospermia Genetics 030219 obstetrics & reproductive medicine Multidisciplinary Base Sequence luteinizing hormone/choriogonadotropin receptor Alternative splicing Intron Exons Receptors LH medicine.disease Alternative Splicing 030104 developmental biology RNA splicing Female RNA Splice Sites |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep45699 |
| Popis: | Selective splicing is a feature of luteinizing hormone receptor (LHCGR). A cryptic exon (LHCGR-exon 6A) was found to be derived from alternative splicing in intron 6 of the LHCGR gene, which including two transcripts LHCGR-exon 6A-long and LHCGR-exon 6A-short. We addressed the functional consequences of SNP rs68073206, located at the +5 position of an alternative 5′ splice donor site, and observed its association with male infertility in the subjects with azoospermia, oligoasthenozoospermia and normozoospermia. The translation product of splicing variant LHCGR-exon 6A was expressed in the cytoplasm and exhibited no affinity with [125I]-hCG. No dominant negative effect was observed in cells co-expressed with LHCGR-exon 6A and wild-type LHCGR. The long transcript (LHCGR-exon 6A-long) was significantly elevated in the granulosa cells with G/G genotypes, which could be reproduced in vitro by mini-gene construct transfection. Genotyping analysis showed no association between rs68073206 and male infertility. However, this polymorphism was significantly associated with testosterone levels in normozoospermic subjects (n = 210). In conclusion, SNP rs68073206 in the splicing site of the cryptic exon 6A of the LHCGR gene affect the splicing pattern in the gene, which may play a role in the modulation of the LHCGR sensitivity in the gonads. |
| Databáze: | OpenAIRE |
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