Effect of estrogen receptor alpha gene polymorphism on the variations of T lymphocyte subsets and its related cell factors in female patients with primary cholestasis cirrhosis

Abstract

To study the effects of estrogen receptor (ER) alpha gene polymorphism on the migration of T lymphocyte subsets and related cytokines in the female patients with primary biliary cirrhosis(PBC). This study was conducted with sixty female PBC patients without treatment as the study group and fifty-two healthy people wtih sex and age met the requirements of the study as the control group. The polymorphism of restriction enzyme cutting site of Xba I and Pvu II in intron 1 of ERa gene was detected by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). CD4+, CD8+, CD4+CD25+ and CD4+CD28- T lymphocytes in peripheral blood were quantitatively detected by flow cytometry. RT-PCR method was used to detect the expression of TNFa, IL-2, IFNgamma, IL-4, IL-6 and IL-10 in peripheral mononuclear cells. The positive rate of Pp in ERa gene Pvu II enzyme gene subtypes of female PBC patients was significantly greater than that of the control group, and the positive rate of pp gene subtype was significantly smaller than that of the control group (X2 = 7.2880, P = 0.0261). The difference of Xba I genotype and allele frequency between the female PBC patients group and the control group was not of statistical significance (X2 = 6.5382, P = 0.5833). The proportion of CD4+ T in T lymphocytes of PBC patients was increased to 45.31%+/-5.26%, compared with 33.81%+/-3.87% in the control group; and the proportion of CD8+ T lymphocytes was decreased to 27.78%+/-1.43 % from 31.83%+/-1.73% in the control group. In comparison with the control group, the proportion of CD4+CD25+ T lymphocytes decreased significantly, while that of CD4+CD28- T lymphocytes rose significantly. The expression levels of TNFa, IL-2 and IFNgamma mRNA were 0.59+/-0.19, 0.71+/-0.29 and 0.67+/-0.21 respectively, which were significantly higher than that in the control group (0.22+/-0.13, 0.31+/-0.14, 0.27+/-0.13) (t = 6.93, 5.07, 7.01, P value less than 0.01); the expression level of IL-6 mRNA was increased to 0.45+/-0.21 from 0.34+/-0.16 in the control group (t = 1.84, P value less than 0.05); and the difference of the expression levels of IL-4 and IL-10 mRNA between two groups was not of statistical significance. Pp of gene Pvu II was a genetically susceptible genotype in female PBC patients, and the allele p was a susceptible gene. Th1 cell subsets and related cytokines were dominant in peripheral blood of PBC patients. As a background of genetic susceptibility, ERa gene polymorphism could affect the shift of T lymphocyte subsets and the expression of the related cytokines in PBC patients.