Kiss1和GPR54基因多态性与多囊卵巢综合征相关性分析

本研究旨在探讨Kiss1和GPR54基因多态性与多囊卵巢综合征的相关性。利用超声检查卵巢体积、血清睾酮、游离雄激素指数情况;临床评估患者身高(cm)和体重(kg)、BMI、静息血压、痤疮和黑棘皮病的分布;ELISA酶联免疫法检测血清中的kisspeptin和睾酮水平,使用Next generation sequencing方法(LGC group, Germany)对基因(Kiss1, GPR54)进行测序。结果显示,PCOS患者比对照组女性具有更高的BMI和mFG评分,PCOS患者血清Kisspeptin和睾酮浓度显著提高,且LH浓度也显著高于对照组(p<0.05)。GPR54和Kiss1 2个基因在患者体内存在多态性;测序分析结果显示GPR54基因存在的2个新的SNP位点(chr19:918686, A→G和chr19:918735, A→G),这2个新的多态性位于内含子区域(内含子2),Kiss1基因也存在两个SNP,位于非翻译变体5的末端(rs5780218)和外显子3 (rs4889),即GPR54基因存在A→G多态性,Kiss1基因为CTT→CT/G→C多态性,且相关性关联分析结果表明,GPR54基因型多态性(Chr19:918735)与PCOS风险增加相关(p<0.05);而Kiss1 SNP的基因型与PCOS风险之间没有关联。此外,PCOS与GPR54和Kiss1基因的单倍型没有显著关联。本研究推论对PCOS发生风险的遗传影响可能不仅是通过直接改变Kiss1/GPR54相互作用,而且还可能通过改变个体与环境因素的相互作用。

Association between Kiss1 and GPR54 Gene Polymorphisms with Polycystic Ovary Syndrome

The aim of this study was to explore the association between Kiss1 and GPR54 gene polymorphisms and polycystic ovary syndrome. Ultrasound was used to check ovarian volume, serum testosterone, free androgen index;ELISA was used to detect kisspeptin and testosterone levels in serum, and next generation sequencing(LGC group, Germany) Perform for sequencing. The results showed that PCOS patients had higher BMI and mFG scores than women in the control group. Serum Kisspeptin and testosterone concentrations in PCOS patients increased significantly, and LH concentrations were significantly higher than those in the control group(p<0.05). GPR54 and Kiss1 genes do have polymorphisms in patients, and then the sequencing analysis showed that the two SNPs present in the GPR54 gene are new(chr19: 918686, A→G and cr19: 918735, A→G). These two new polymorphisms are located in the intron region(intron 2). There are also two SNPs in the Kiss1 gene, located at the end of untranslated variant 5(rs5780218) and exon 3(rs4889), that is, the sequencing results of GPR54 and Kiss1 genes showed that there was an A →G polymorphism in GPR54 gene and a CTT →CT/G →C polymorphism in Kiss1 gene, and the correlation analysis showed that the GPR54 genotype polymorphism(Chr19: 918735) was associated with increased PCOS risk(p<0.05);there was no association between the genotype of Kiss1 SNP and PCOS risk. In addition, PCOS was not significantly associated with haplotypes of the GPR54 and Kiss1 genes. We conclude that the genetic impact on the risk of PCOS may be through not only directly altering the Kiss1/GPR54 interaction, but also by altering the interaction of any given individual with environmental factors.