Study On The Relationship Between Ghrelin Gene And Polycystic Ovary Syndrome And Its Related Obesity

ObjectiveTo study the relationship between Ghrelin gene locus and polycystic ovary syndrome and its associated obesity.MethodIn this study,230 patients with PCOS treated in the Department of Gynecology of the affiliated Hospital of Qingdao University from January 2017 to December 2018 were collected as the case group.In the same period,162 normal women who were infertile due to male factors were selected as the control group.The fasting peripheral venous blood of all subjects were collected in the morning,and the levels of sex hormones were detected by electrochemiluminescence(ECL).At the same time,the extracted DNA was targeted to capture the full-length site of Ghrelin gene by multiplex polymerase chain reaction(M-PCR).The Ghrelin gene site was sequenced by high-throughput sequencing technology,and the correlation of the sequencing data was analyzed.Results1.There was no significant difference in age and levels of estradiol(E2),testosterone(T)and prolactin(PRL)between PCOS group and control group.The body mass index(BMI),luteinizing hormone(LH)and waist-to-hip ratio(WHR)in the PCOS group were significantly higher than those in the control group(P<0.001).Compared with the control group,the level of follicle stimulating hormone(FSH)in PCOS patients was significantly lower(P<0.001).2.Twenty-four loci were identified by high-throughput sequencing,including rs696217,rs34911341 in exon region and rs26802 and rs27647 in promoter region.The association analysis of these four loci and intron region rs35681 and rs2075356 showed that there was significant difference in genotype frequency of rs35681 in dominant model(OR=2.28;95%CI:1.081?4.808;P=0.028),but no significant difference was found in additive model and recessive model.3.GG and GA genotypes of rs35681 locus were significantly different between BMI and WHR in the comparison of general clinical characteristics of patients with PCOS.The level of LH in patients with PCOS was significantly higher than that in the control group(P=0.024;P=0.002),but there was no significant difference in other clinical indexes between the two groups.4.Hardy-Weinberg equilibrium test(X~2=1.119,P=0.29)analyzed the genotype-phenotypic correlation of rs35681 locus,which showed that the locus was representative of the population.There was a significant difference in the An allele of rs35681 between the polycystic ovary syndrome group and the control group(P=0.024).5.Haplotype analysis of SNPs showed that the prevalence of AACGAA was higher in patients with polycystic ovary syndrome,suggesting that AACGAA was associated with the risk of polycystic ovary syndrome(OR=5.606,95%CI:1.430?21.976,P<0.05).6.There were significant differences in rs35681 genotypes and alleles between the obese group and the control group(P=0.013,P=0.017)),but there was no significant difference between the non-obese group and the obese group(P>0.05).The proportion of An allele in the obese group(10.9%)was higher than that in the non-obese group(3.7%).Conclusion1.No direct correlation was found between Ghrelin gene locus polymorphism and PCOS,but this gene locus was associated with the occurrence of PCOS-related obesity.2.Ghrelin gene rs35681 may be associated with PCOS-related obesity,and allele A may be a high risk factor for PCOS obesity.