Association Study About Polymorphisms, Gene-gene Interaction Of ER And DNMT3B And Depressive Disorder In Chinese Han Perimenopausal Women

【Objective】 The study aimed to explore the role of polymorphism of estrogen recepter gene,DNA methyltransferase 3B gene and interaction between two genes to the susceptibility of depressive disorder in perimenopausal women. Also analysis preliminaly of DNA methylatic epigenetic modification to ER gene in the role of reproductive cycle related depression.【Method】 1. 403 were randomly selected from 3284 perimenopausal women 45~55 years of age attending three gynecological clinics and one psychological clinic in Shanghai.Respondents completed our self-designed investigation questionnaires for demographic profile,personal history of gynaecology and obstetrics and scales including The Beck’s depression inventory scale(BDI).2. The Beck’s depression inventory(BDI) and SCID-I/P were used to screen the depressive symptoms and diagnose the depressive disorder. 3. 403 of all the respondents which including 65 patients diagnosed as depressive disorder and 122 matching controls were analyzed on the polymorphism of thress tag SNPs in estrogen beta receptor gene and the polymorphism of two tag SNPs in DNA methyltransferase 3B gene.【Result】 1. No statistically significant differences(p>0.05) in alleles, genotypes, and haplotypes distribution of ER-β and DNMT3 B between patients and healthy controls were detected. 2. The genotype of C/C in rs1256031 polymorphism of ER-β gene was positive correlated to quantitative trait of depressive symptoms(Add value =3.66,95%CI=1.17～6.15,p=0.007),but G/A in rs1256062 polymorphismwas negative correlated(Add value=-2.90,95%CI=-4.87～-0.92,p=0.015). The haplotype of CA jointed by rs1256031 and rs1256062 polymorphism,AA jointed by rs1269056 and rs1256062 polymorphism,GC jointed by rs1269056 and rs1256031 polymorphism,and GCA by above three Single nucleotide sequences polymorphism was positive correlated to quantitative trait of depressive symptoms(Add value =1.69, 1.49, 2.28, 2.68;95%CI=0.37～3, 0.11～2.87, 0.23～4.34, 0.44～4.19;p=0.012,0.035, 0.03, 0.019)with the strong linkage disequilibrium existent(D’ >0.5, r2>0.33). 3. The haplotype of TC jointed by rs6141813 and rs2424908 polymorphism of DNMT3 B gene was positive correlated to quantitative trait of depressive symptoms(Add value =2.45; 95%CI=0.14~1.75; p=0.038) with the strong linkage disequilibrium existent(D’=0.983,r2=0.624). 4. The gene-gene interaction between ER gene( including ER-α gene and ER-β gene) with DNMT3 B gene were significantly associated with the occurrence of the disease,the best gene-gene interaction model stablished by MDR software were including PvuⅡ, rs1269056 and rs6141813 polymorphism(X2=22.1, p < 0.0001).【Conclusion】 1. Polymorphism of both ER-β gene and DNMT3 B genes may have association with quantitative trait of depressive disorder in perimenopausal women.2. Interaction of ER(ER-β and ER-α)gene with DNMT3 B gene may be determined and revealed a deleterious genetic combination that enhances the risk of the disease.