Association Of LHCGR Gene SNPs And Serum LHCGR Level With Polycystic Ovary Syndrome

Objective:（1）To investigate the association between Luteinizing hormone receptor（LHCGR）levels in peripheral blood and polycystic ovary syndrome（PCOS）.（2）To investigate the association between LHCGR gene rs4519576,rs2293275,rs10495960 and rs4953616 polymorphisms and susceptibility to PCOS.（3）Analyze the correlation between LHCGR gene polymorphisms and the serum expression levels of LHCGR.Methods:（1）The study subjects included 234 PCOS patients and 248 controls.We used enzyme-linked immunosorbent assay（ELISA）to detecte serum expression levels of LHCGR for all subjects.（2）The im LDR^TMSNP was used to detected the genotypes of LHCGR gene rs4519576,rs2293275,rs10495960 and rs4953616,and the DNA sequencing was used to validated the genotyping results.Results:（1）The serum LHCGR levels in PCOS and control group were 13.73（1.08-47.20）ng/m L and13.38（2.11-48.58）ng/m L,respectively.There was no significant difference between two groups（P>0.05）.LHCGR serum levels in different subgroups of PCOS patients:Obese and non-obese group were 13.31（3.60-41.06）ng/m L and 13.95（1.08-47.20）ng/m L,respectively.Hyperandrogenesis and normal androgen group were 13.47（1.08-41.06）ng/m L and 14.40（1.08-47.20）ng/m L,respectively.Insulin resistance and non-insulin resistance group were 13.73（1.08-39.56）ng/m L and12.86（1.08-47.20）ng/m L,respectively.LH/FSH≥2 and LH/FSH?2 group were 13.57（1.08-47.20）ng/m L and 13.84（1.08-41.06）ng/m L,respectively.There was no significant difference of serum LHCGR levels between subgroups（P>0.05）.（2）Allele frequencies of LHCGR gene rs4519576,rs2293275,rs10495960 and rs4953616 were not significantly different between the PCOS and control groups（P>0.05）.（3）Genotype frequency of rs4519576 CT in PCOS group was lower than that in control group,there was significant difference between two groups（CT vs.TT:OR=0.54,95%CI,0.32-0.92,P=0.023）,and there was still statistical difference after correcting by age and BMI（CT vs.TT:adjusted OR=0.55,95%CI,0.31-0.96,P=0.034）.Genotype frequency of rs4519576 CT/CC in PCOS group was lower than that in control group,there was significant difference between two groups（CT/CC vs.TT:OR=0.57,95%CI,0.34-0.96,P=0.033）,however,there was no statistical difference after correcting by age and BMI（CT/CC vs.TT:adjusted OR=0.59,95%CI,0.34-1.02,P=0.056）.Additionaly,genotype frequencies of rs2293275,rs10495960 and rs4953616 were not significantly different between the PCOS and control groups（P>0.05）.（4）Genotype and allele frequencies of rs4519576 in OA,HA,PCO group and control group were not statistically significant（P>0.05）.（5）Endocrine and metabolic indicators and LHCGR levels in different genotypes of rs4519576were no significant difference（P>0.05）.（6）The distribution frequencies of haplotype T-C-G-T in PCOS and control group were 44.9%and 37.1%,and the haplotype T-C-G-T may increase the risk of PCOS（OR=1.41,95%CI,1.08-1.83,P=0.010）.Conclusion:（1）PCOS is not associated with LHCGR expression in serum and LHCGR has not been used as an indicator to distinguish PCOS patients with different standard classifications.（2）LHCGR gene rs4519576 polymorphisms are related with PCOS,CT genotype is correlated with the reduction of PCOS risk.（3）haplotype T-C-G-T consist of rs4519576,rs2293275,rs10495960 and rs4953616 may increase the risk of PCOS.