Molecular Endocrinology, Functional Genomics & System Biology Laboratory, Animal Biochemistry Division, ICAR - National Dairy Research Institute, Karnal, India.
Centre for Agricultural Bioinformatics, ICAR-Indian Agricultural Statistics Research Institute, New Delhi, India.
Gene. 2022 Aug 5;834:146580. doi: 10.1016/j.gene.2022.146580. Epub 2022 May 19.
Thyrotropin releasing hormone degrading enzyme (TRHDE) gene is implicated in Thyrotropin releasing hormone (TRH) mediated prolactin secretion. It has been shown that the prolactin secretion alters the Gonadotropin-releasinghormone(GnRH) mediated estrous cycle. Therefore, TRHDE may also regulate postpartum anestrus. Earlier studies reported the role of non-synonymous single nucleotide polymorphism (SNPs) in various pathophysiological conditions by altering the structure and function of the proteins. Hence, in the present study, we identified SNPs in the putative promoter, first exon, middle exon and 3'-UTR containing the last exon of TRHDE gene and determined their association with postpartum anestrus (PPA) in Murrah buffaloes. We found one non synonymous SNP (G > C at 118095875 bp on chromosome 4) in the first exon of TRHDE and performed its association analysis in a population sample of 50 extreme PPA (residual PPAI: 123.06 ± 12.98 days) and 50 normal (residual PPAI: -80.46 ± 3.19 days) buffaloes. The residual PPAI value was the observed PPAI adjusted for the effect of 38 non-genetic factors. The analysis showed a significant (P < 0.004167) association of this SNP with PPA in buffaloes. Molecular dynamics simulations (MDS) also supported that the C allele altering Glutamine to Histidine at the amino acid 148 of TRHDE could enhance the stability and rigidity of TRHDE protein, which may lower its activity, increase TRH and prolactin, and reduce GnRH in PPA buffaloes. The MDS analysis further strengthens the association of the SNP (G > C) in the TRHDE gene with PPA condition in Murrah buffaloes. However, further investigation is needed to prove the MDS observations.
促甲状腺素释放激素降解酶（TRHDE）基因参与促甲状腺素释放激素（TRH）介导的催乳素分泌。已经表明，催乳素分泌会改变促性腺激素释放激素（GnRH）介导的发情周期。因此，TRHDE 也可能调节产后乏情。早期的研究表明，非 synonymous单核苷酸多态性（SNPs）通过改变蛋白质的结构和功能，在各种病理生理条件下发挥作用。因此，在本研究中，我们鉴定了 TRHDE 基因的假定启动子、第一外显子、中间外显子和包含最后外显子的 3'-UTR 中的 SNPs，并确定了它们与摩拉水牛产后乏情（PPA）的关联。我们在 TRHDE 的第一外显子中发现了一个非同义 SNP（G > C 位于第 4 号染色体上的 118095875 bp），并在一个由 50 个极端 PPA（残留 PPAI：123.06 ± 12.98 天）和 50 个正常（残留 PPAI：-80.46 ± 3.19 天）水牛组成的群体样本中进行了关联分析。残留 PPAI 值是在考虑 38 个非遗传因素影响后观察到的 PPAI 值。分析表明，该 SNP 与水牛 PPA 之间存在显著关联（P < 0.004167）。分子动力学模拟（MDS）也支持 TRHDE 中第 148 位氨基酸由谷氨酰胺变为组氨酸的 C 等位基因，可以增强 TRHDE 蛋白的稳定性和刚性，从而降低其活性，增加 TRH 和催乳素，减少 GnRH 在 PPA 水牛中的含量。MDS 分析进一步加强了 TRHDE 基因中 SNP（G > C）与摩拉水牛 PPA 状况的关联。然而，需要进一步的研究来证明 MDS 观察结果。
