白细胞介素-6基因启动子多态性与子宫内膜异位症的相关性分析

Correlation of the polymorphism of interleukin-6 (IL-6) gene promoter with morbidity of endometriosis

目的研究白细胞介素-6(IL-6)基因启动子-174G/C、-572C/G及-597G/A的多态性在子宫内膜异位症(EM)患者及非EM育龄女性(对照组)中的分布。方法采用病例对照研究的方法,选取98例EM患者,其中轻、中、重型(即Ⅱ、Ⅲ、Ⅳ期)分别为22、35、41例,以99名非EM育龄女性外周血白细胞为对照,应用聚合酶链反应-限制性片段长度多态性技术检测IL-6基因启动子-174、-572及-597的多态性,比较两组IL-6启动子基因型和等位基因的分布频率,对两组间基因多态性存在明显差异的基因位点进行组间比较。结果IL-6基因启动子-174位点的GG、CG和CC基因型在EM组中分别为100%、0%、0%,在对照组中分别为98.99%、1.01%、0%,两组的分布频率差异无显著性;-572位点的CC、CG和GG基因型在EM组中分别为55.10%、42.86%、2.04%,在对照组中分别为70.71%、28.28%、1.01%,两组的基因分布频率差异有显著性;所有实验对象-597位点的基因型均为GG型,两组均无GA及AA基因型存在;-572位点的CC、CG和GG基因型在轻型EM组中分别为59.09%、40.90%、0%,在中型EM组中分别为54.29%、42.86%、2.85%,在重型EM组中分别为53.66%、43.90%、2.44%,轻、中、重组间基因型及等位基因分布频率无明显差异。结论IL-6基因启动子的-174位点变异率极低,-597位点末发现变异,以上两位点基因变异与EM的发病无明显相关性;而启动子-572位点的多态性分布与EM的发病具有一定程度的相关性,但与疾病的严重程度无关。

Objective To detect the distribution of site -174G/C, site -572C/G and site -597G/A of interleukin-6 gene promoter regions in patients with endometriosis, and to analyze polymorphism of the promoter. Methods Interleukin-6 gene promoter region polymorphism was detected by polymerase chain reaction- restriction fragment length polymorphism in patients with endometriosis （n= 98） and normal controls （n=99）. Among the 98 patients with endometriosis, 22 were defined as stageⅡ, 35 as stage Ⅲ and 41 as stage IV. Comparisons between the two groups on the genotype of IL-6 gene promoter and the distributed allele frequency were done, and also among the patients of stageⅡ, Ⅲ and Ⅳonce significant differences were detected in genotype frequency or allele frequency in disease group and control group. Results At the site -174, the frequencies of GC-,GC and CC genotypes were 100%, 0% and 0%, respectively, in patients with endometriosis, while 98. 99%, 1.01% and 0%, respectively, in normal controls. No significant difference was found in the distribution frequency of IL-6 genotype between patients with endometriosis and normal controls. At the site -572, the frequencies of CC, CG and GG genotypes were 55. 10%, 42. 86% and 2. 04%, respectively, in patients with endometriosis, while they were 70. 71%, 28. 28% and 1.01%, respectively, in normal controls. A significant difference existed between the two groups. At the site -597 of IL-6 gene, no GA and AA genotypes were found in the two groups. At the site -572, the frequencies of CC, CG and GG genotypes were 59. 09%, 40. 90% and 0%, respectively, in patients with endometriosis of stage Ⅱ , 54. 29%, 42. 86% and 2. 85% in patients of stage Ⅲ, and 53. 66%, 43. 90% and 2. 44% in patients of stage Ⅳ. No significant difference was found among the three groups. Conclusion Mutations at the sites -174 and -597 of IL-6 gene promoter region were rare. Their distribution frequencies have nothing to do with morbidity of endometriosis. While at the site -572, its distribution frequency of genotype shows correlation with morbidity of endometriosis but does not show correlation with the extent of endometriosis.