title: Polymorphism in the Alternative Donor Site of the Cryptic Exon of LHCGR: Functional Consequences and Associations with Testosterone Level.
abstract: 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.
authors.affiliation: Department of Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.affiliation: Department of Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Wenjiao
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Cheng
authors.affiliation: Research Center for Clinical Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Mengxia
authors.initials: M
authors.lastname: Fan
authors.affiliation: Department of Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jiajun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Reproductive Centre, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Reproductive Centre, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jiqiang
authors.initials: J
authors.lastname: Si
authors.affiliation: Reproductive Centre, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Lyu
authors.affiliation: Reproductive Centre, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Weiran
authors.initials: W
authors.lastname: Chai
authors.affiliation: Research Center for Clinical Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Shuangxia
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Research Center for Clinical Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Huaidong
authors.initials: H
authors.lastname: Song
authors.affiliation: Reproductive Centre, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Kuang
authors.affiliation: Department of Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Qiao
mesh_terms: D017398:Alternative Splicing; D001483:Base Sequence; D005091:Exons / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007248:Infertility, Male / Q000235:genetics / Q000378:metabolism; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D022821:RNA Splice Sites / Q000235:genetics*; D011974:Receptors, LH / Q000235:genetics*; D013739:Testosterone / Q000378:metabolism*
chemical_list: D022821:RNA Splice Sites; D011974:Receptors, LH; D013739:Testosterone