The CpG Island Methylation Status Of LMNA Gene In Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is the most common endocrine disorders in women of reproductive age. Now it recognized as a high genetic heterogeneous disorder that results in hyperandrogenism, polycystic ovaries, chronic anovulation, insulin resistance and abdominal obesity. Long-term sequellae of PCOS include higher risk for diabetes, metabolic syndrome and anovulatory infertility. The etiology of syndrome is not well known so far. Genetics and environment factors can not absolutely explain the syndrome. At present, it has been accepted that epigenetics is involved in the development and inheritance of PCOS. Currently, increasing attention has been paid on the role of epigenetics in the development of polycystic ovary syndrome, and the pathogenesis of polycystic ovary syndrome has become a popular direction of interest of scholars home and abroad.This study included2parts, as follows:1.basic research, gene methylation chip screening was done in3cases of insulin resistant PCOS patients and1case of normal woman. The high incidence of methylated genes,which might be related to PCOS was selected, and the results were verified.2. clinical research, Using MassARRAY(?) EpiTYPERTM DNA methylation analysis techniques to measure hypermethylation of selected genes in48cases of insulin resistant PCOS patients and controls. This study is designed to discover and identify genes of high incidence of methylation and its relationship with PCOS, and to provid theoretical basis for the epigenetic changes of PCOS.Section I Foudation researchObjective Gene chip methylation screening was done on3cases of insulin resistant PCOS patients and1case of normal woman. The high incidence of methylated genes which might be related to PCOS were selected, and the results of the chips were verified.Methods The Roche-NimbleGen methylation microarray was done on the blood samples of3insulin resistant PCOS patients and1case of normal woman to detect the level of gene methylation. MassARRAY(?) EpiTYPERTM DNA methylation analysis techniques was used to verify the chip results.Results The CpG island of the promoter regions of the three gene RPS4X, KCNJ11and LMNA had hypermethylation changes, but verified analysis found that only the promoter CpG island of LMNA gene had hypermethylation changes.Conclusion The methylation status of LMNA gene changes might play some role in the pathogenesis of PCOS.Section II Clinical ResearchObjective To investigate the LMNA gene methylation status in PCOS patients and normal controls, and to find changes in LMNA gene methylation status and its association with PCOS.Methods The MassARRAY(?) EpiTYPER TM DNA methylation analysis techniques were used to detect LMNA gene CpG island methylation of20sites in the two groups.Results The site of LMNA gene CpG island methylation was changed, among which,12CpG sites were different between the PCOS patients and control, and the remaining8CpG sites was of no difference between the two groups.Conclusion Promoter hypermethylation of LMNA gene in human might be associated with PCOS.Summary1The CpG island of the promoter regions of the three gene RPS4X, KCNJ11and LMNA had hypermethylation changes, but verified analysis found that only the promoter CpG island of LMNA gene had hypermethylation changes.2The site of LMNA gene CpG island methylation have changed, among which,12CpG sites were different between the PCOS patients and control, and the remaining8CpG sites was of no difference between the two groups. Promoter hypermethylation of LMNA gene in human might be associated with PCOS...