Association Of PPAR-γ2 Gene Pro12Ala Polymorphism With Endometriosis

Objective: Endometriosis(EMs) is one of the most common and frequently-occurring disorders of reproductive aged women. The incidence reaches 10%-15%. With the development of society,the incidence of infertility is increasing in recent years.This disease can bring chonic pelvic pain,dysmenorrhea and infertility for women,and jeapardizes seriously the physical and mental health of vast reproductive age femal.It is a research highlight of gynecology to investigate exact causes and pathogenesis of endometriosis.The eutopic endometrium determinism which is put forward in the international arena consider that the occurrence of endometriosis is base on different biological characteristic of eutopic endometrium even the genetic differences.Peroxisome proliferator activated receptors(PPARs) are transcripts which are members of the nuclear hormone receptor family. PPARs can activate transcription and initiate hundreds of target genes expression through heterodimerizing with the alitretinoin receptor after combining the ligand at the promoter region of target genes.There are three hypotype in the PPARs thus far,and they are PPAR-α,PPAR-βand PPAR-γ. PPAR-αwhich is expression in brown adipose tissue and liver is a major player in the lipid metabolism; PPAR-βis found in various tissues, a hypotype: PPAR-γ1 and PPAR-γ2. PPAR-γ2 which is expression in various tissues can inhibit the reaction of inflammation. PPAR-γ2 gene mutations may result in protein conformation changes which lead to decrease of protein activity and can't inhibit the reaction of inflammation.In studies published elsewhere, PPAR-γ2 gene may have association with genetic predisposition to endometriosis. The PPAR-γ2 gene is located on 3p25.Several genetic variants in the PPAR-γ2 gene have been described, the most prevalent being the Pro12Ala polymorphism in PPAR-γ2. It is the result of a CCA-to-GCA missense mutation in codon 12 of exon B of the PPAR-γ2 gene. This missense mutation make proline into alanine,which is called Pro12Ala polymorphism. In studies in vitro, PPARγcould suppress monocyte cells attracted into the inflamed peritoneal cavity in women with endometriosis.It is deemed to be advantageous to growth of ectopic endimetrium. PPAR-γ2 gene mutations may result in protein conformation changing which lead to decrease of protein activity and can't inhibit the reaction of inflammation,then the effect that PPAR-γsuppresses activation of monocytes reduces.Thus, In theory individuals who carry these mutations may be particularly susceptible to endometriosis. We evaluated whether the Pro12Ala polymorphisms and its haplotypes polymorphisms in PPAR-γ2 is associated with the risk of moderate/severe endometriosis.Methods: Group of patients with endometriosis: A total 134 women between 20 and 45 years old undergoing laparotomy or laparoscopy for endometriosis in the Department of Obstetrics and Gynecology of the Second Affiliated Hospital of Hebei Medical University. Diagnosis of endometriosis was establishied laparoscopically and histologically. In clinical practice, most women with minimal/mild endometriosis accept conservative medication instead of invasive management. Therefore, we only recruited the moderate/severe endometriosis women for the survey. Control group: 134 women were from non-endometriosis patients who were such conditions as reananstomosis infertility or septate uterus, and without pelvic endometriosis and adenomyosis and adenomyosis evidenced by clinical manifestation,physical sign and assistant examination or laparotomy or laparoscopy, with no history of endometriosis. All patients didn't be attacked by systemic lupus erythematosus,diabetes,rheumatoid arthritis,inflammatory bowel disease,Polycystic ovarian syndrome and obesity, simultaneously didn't take any drugs with hormone or immune suppression .The genomic DNA was prepared from peripheral blood leukocytes by the use of a genomic DNA isolation kit. The DNA was stored at -80℃until analyzed. PPAR-γ2 Pro-12-Ala fragment was amplified by polymerase chain reaction--restriction fragment length polymorphism (PCR-RFLP) method. After PCR amplification, the PCR products were digested at with specific restriction enzyme to detect PPAR-γ2 Pro12Ala C/G allele, then subjected to 1.5% agarose gel electrophoresis and visualized under ultraviolet light. Statistical analysis was performed using SPSS13.0 software package. Two-tailed test with P<0.05 were considered significant.Results:1 Hardy-Weinberg analysis was performed to compare the observed and expected genotype frequencies using Chi-square test, finally shows P>0.05, indicated in choosing the community the candidate gene has reached the heredity balance.2 Among 134 patients with stageⅢ,Ⅳendometriosis and 134 controls,proportions of PPAR-γ2 Pro12Ala CC,CG,GG genetype in the group of endometriosis were: 89.55/9.70/0.75% , and in the control group were 93.28/5.97/0.75%, respectively(χ2=1.513,P=0.681).No association between PPAR-γ2 Pro12Ala polymorphisms andⅢ,Ⅳendometriosis was found. Proportions of PPAR-γ2 Pro12Ala CC,CG+GG genetype in the group of endometriosis were: 89.55/10.45%, and in the control group were 93.28/6.72%, respectively OR=0.617(95%CI=0.258-1.479). No differences was also found between the two groups. This indicated that PPAR-γ2 Pro12Ala polymorphisms may not be an independent risk factor in endometriosis development.Conclusion: There was no association between PPAR-γ2 Pro12Ala polymorphism and stageⅢ,Ⅳendometriosis.