Associations of the KiSS-1 and GPR54 genetic polymorphism with polycystic ovary syndrome in Yunnan, China

Abstract

Bsckground

Polycystic ovary syndrome (PCOS) is a heterogeneous condition that increases the risk for serious health complications among women. Thus, in this study, we aimed to identify polymorphisms in the KiSS-1 and GPR54 genes and investigate the associations between KiSS-1, BMI, FSH, LH, and estradiol in Chinese women with PCOS.

Methods

This study recruited women with PCOS (n = 60) and controls (n = 60). We collected blood samples and measured endocrine indicators (kisspeptin, FSH, LH–FSH ratio, estradiol, prolactin, and testosterone). PCR and Snapshots were performed to screen single nucleotide polymorphisms (SNPs) of the KiSS-1 and GPR54 genes.

Results

Compared with the controls, endocrine and metabolic disturbances in women with PCOS were reflected in significantly higher levels of BMI, LH, LH–FSH ratio, prolactin, and testosterone. Serum kisspeptin levels were significantly higher and positively correlated with LH and T levels (p < 0.05). No identified SNPs of KiSS-1 and GPR54 showed significant differences in frequency between patients and controls. The mutant G allele was highly predisposed to polymorphism in the PCOS GPR54 gene r10407968. We observed a significant difference in estradiol (p = 0.023, p = 0.012) after comparing the values of LH, FSH, estradiol, progesterone, and testosterone among the three genotypes of rs4889 and rs5780218. The KiSS-1 rs4889 CC genotype and rs5780218 AA genotype showed significantly higher estradiol levels compared with the other two genotypes.

Conclusions

These results suggest that kisspeptin plays a potential role in the etiology of PCOS.

摘要

背景

多囊卵巢综合征（polycystic ovary syndrome, PCOS）是一种异质性疾病, 会增加女性严重健康并发症的风险。因此, 在本研究中, 我们旨在调查KiSS-1和GPR54基因的多态性, 并研究PCOS患者KiSS-2、BMI、FSH、LH和雌二醇之间的关系。

方法

本研究招募了PCOS患者（n=60）和对照组（n=60）。我们收集血液样本并测量内分泌指标（kisspeptin, FSH, LH-FSH比值, 雌二醇, 催乳素和睾酮）。进行PCR和Snapshots以筛选KiSS-1和GPR54基因的单核苷酸多态性（single nucleotide polymorphisms, SNPs）。

结果

与对照组相比, PCOS患者的内分泌和代谢紊乱反映在BMI、LH、LH-FSH比值、催乳素和睾酮水平显着升高。血清kisspeptin水平显著升高, 与LH和睾酮水平呈正相关（p<0.05）。未发现KiSS-1和GPR54的SNPs在患者和对照之间显示出频率上的显著差异。突变G等位基因高度倾向于PCOS GPR54基因r10407968多态性。在比较rs4889和rs5780218的三种基因型中LH, FSH, 雌二醇, 孕酮和睾酮的值后, 我们观察到雌二醇的显著差异（p=0.023, p=0.012）。与其他两种基因型相比, KiSS-1 rs4889 CC基因型和rs5780218 AA基因型雌二醇水平显著升高。

结论

这些结果表明, kisspeptin 在 PCOS 的病因学中起潜在作用。

Keywords:

• KiSS-1 gene
• Kisspeptin
• LH
• FSH
• PCOS

关键词:

• 卵泡刺激素
• KiSS-1基因
• Kisspeptin
• 黄体生成素
• 多囊卵巢综合征

Disclosure statement

None of the authors have any potential conflicts of interest associated with this research.

Ethics approval and consent to participate

This study was approved by the Ethical Research Committee at the First People’s Hospital of Yunnan Province (approval number: 2018FE117). Written informed consent was obtained from the participants and in the case of minors, informed consent was granted from their legally authorized representatives with the option to withdraw them from the study at any time.

Additional information

Funding

This work received financial support from the Basic Research Program of Yunnan Province (2019FE001-174, 2018FE117, 202001AY070001-115); the Talent Development Program of Yunnan Province (D-2018054); Major Science and Technology Projects (2019ZF004-1-5).