Study On The Association Of SNPs Of FAS And FASL Genes With The Risk Of Endometriosis

Objective: Endometriosis (EM) is an invasive but benign gynecologicaldisease, characterized by the presence and growth of endometrial glandularand stromal cells outside the uterine cavity. The etiology and pathogenesis ofendometriosis remain obscure to date. Recently, studies showed that theFAS/FASL system is a major pathway for the induction of apoptosis andcontributes to the turnover of normal endometriosis. Decreased expression ofFAS and/or elevated expression of FASL have been detected in a variety ofcancers, and play an important role in the development and progression ofcancer. Endometriosis can behave like a malignancy in terms of growing,infiltrating and adhering to the surrounding tissues, and the abnormalexpression of FAS and FASL had also been found in EM. It has been showedthat the FAS-1377G/A, FAS-670A/G and FASL-844T/C polymorphismsmight influence the transcriptional level of the two genes and have an effecton their expression alteration. These polymorphisms have been linked to anincreased risk of certain cancers. Considering the important functions of FASand FASL on the development of cancer, we conducted a study to test whetherthe three SNPs in the promoter regions of FAS and FASL genes may beassociated with the risk of endometriosis.Methods: This case-control study consisted of486women with endome-triosis and493healthy women as control. Venous blood（5ml） was drawnfrom each subject into vacutainer tubes containing EDTA and stored at4℃.Genomic DNA was extracted within one week after sampling using proteinaseK digestion followed by a salting out procedure. The FAS-1377G/A, FAS-670A/G and FASL-844T/C SNPs were genotyped by polymerase chainreaction-ligase detection reaction (PCR-LDR) analysis.Statistical analysis was performed using SPSS13.0software package. The age difference of cases and frequency-matched controls was analyzed bythe t-test. Hardy–Weinberg analysis was performed by comparing theobserved and expected genotype frequencies in the control group using thechi-square test. Comparison of the FAS and FASL allelotype, genotype,haplotype and combined genotype distribution in endometriosis patients andhealthy controls were performed by means of two-sided contingency tablesusing the chi-square test. The FAS haplotype frequencies and linkagedisequilibrium coefficients were estimated using the EH linkage software and2LD program, respectively. The odds ratio (OR) and95%confidence interval(CI) were calculated using an unconditional logistic regression model. Aprobability level of5%was considered significant for all statistical analyses.Results:1The distribution of the FAS-1377G/A, FAS-670A/G and FASL-844T/C genotypes in controls did not significantly deviate from that expected fora Hardy–Weinberg equilibrium (P>0.05).2The frequencies of the FAS-1377G/A G and A allele among patientswith endometriosis and healthy controls were69.8%,30.2%and71.1%,28.9%, respectively; The distribution of the G/G, G/A, A/A genotypes betweenpatients with endometriosi（s48.6%,42.4%,9.0%）and control（s50.3%,41.6%,8.1%). No significant difference in the FAS-1377G/A allele and genotypedistribution was shown between patients with endometriosis and controls(P>0.05). Compared with the G/G genotypes, the G/A+A/A genotypes couldnot increase the risk of developing endometriosis, the odds ratio was0.93(95%CI=0.73-1.20). Compared with the G/A+G/G genotypes, the A/Agenotype could not increase the risk of developing endometriosis, the oddsratio was1.13(95%CI=0.72-1.76).3The frequencies of the FAS-670A/G A and G allele among patientswith endometriosis and healthy controls were66.0%,34.0%and65.0%,35.0%respectively; No significant difference in the FAS-670A/G alleledistribution was shown between patients with endometriosis and controls(P>0.05). The distribution of the G/G, A/G, A/A genotypes between patients with endometriosis (43.8%,44.5%,11.7%）and controls（40.8%,48.5%,10.7%）also had no significant difference (P>0.05). Compared with the A/Agenotypes, the A/G+G/G genotypes could not increase the risk of developingendometriosis, the odds ratio was1.13(95%CI=0.88-1.46).4The frequencies of the FASL-844T/C C and T allele among patientswith endometriosis and healthy controls were75.9%,24.1%and74.6%,25.4%, respectively; No significant difference in the FASL-844T/C alleledistribution was shown between patients with endometriosis and controls(P>0.05). The distribution of the C/C, C/T, T/T genotypes between patientswith endometriosis (58.2%,35.4%,6.4%）and controls（56.8%,35.7%,7.5%）also had no significant difference (P>0.05). Compared with the C/C genotypes,the C/T+T/T genotypes could not increase the risk of developingendometriosis, the odds ratio was1.06(95%CI=0.82-1.37).5The FAS-1377G/A and-670A/G polymorphisms displayed stronglinkage disequilibrium (D’=0.999998，P＜0.001). But the distribution of theFAS-1377G/A and-670A/G haplotype between patients with endometriosisand controls had no significant difference (P>0.05).6FAS and FASL SNP combined genotype did not significantly affect therisk of developing endometriosis.Conclusions: The results demonstrated no significant association of theFAS-1377G/A,-670A/G and FASL-844T/C SNPs with the genetic risk ofendometriosis.