程序性细胞凋亡1基因单倍型及紫外线暴露与系统性红斑狼疮的相关性研究  

Study on the relationship of the haplotypes of programmed cell death 1 gene and ultraviolet history with systemic lupus erythematosus

作　　者：彭春林[1] 江峰[1] 王宝涛[4] 杨晓惠[4] 齐媛媛[1] 付朝伟[1] 秦万章[2] 许爱娥[5] 吴擢春[3] 孟炜[1] 

机构地区：[1]复旦大学公共卫生学院流行病学教研室,公共卫生安全教育部重点实验室,上海200032 [2]复旦大学公共卫生学院附属中山医院皮肤科,上海200032 [3]复旦大学公共卫生学院社会医学与卫生统计学教研室,公共卫生安全教育部重点实验室,上海200032 [4]苏州大学附属第一医院皮肤科 [5]杭州市第三人民医院皮肤科

出　　处：《中华医学遗传学杂志》2010年第4期417-422,共6页Chinese Journal of Medical Genetics

基　　金：基金项目：国家自然科学基金（30471485）

摘　　要：目的 探讨中国长江以南汉族人群中程序性细胞凋亡1基因（programmed celll death 1,PDCD1）多态性与紫外线暴露在系统性红斑狼疮（systemic lupus erythematosus,SLE）发病中的关系.方法 采用病例对照研究设计,收集159例病例和159名对照,应用聚合酶链反应-限制性片段长度多态技术检测PDCD1基因多态;分别在隐性、显性、相加及共显性遗传模式下,应用Logistic回归模型估计基因、环境及基因-环境交互效应.结果 根据赤池信息量准则（Akaike＇s Information Criteria,AIC）值最小原则,筛出3个相加遗传模式下的最优模型和1个显性遗传模式下的最优模型.控制年龄与性别因素后,4个模型均存在SLE患病人群既往紫外线暴露率高于对照组,差异有统计学意义（P值均＜0.05）.在由PDCD1基因PD1.2、PD1.5及PD1.6多态位点等位基因组成的单倍型方面,在相加遗传模式下,SLE患者人群的G-T-A单倍型频率高于对照组（0.1196 vs 0.0363）,差异有统计学意义（P＜0.05,OR=4.319）;而A-C-A单倍型频率病例组低于对照组（0.4746 vs 0.5399）,差异亦有统计学意义（P＜0.05,OR=0.571）;此遗传模式下,还发现A-C-G单倍型与紫外线暴露存在交互作用,（β5=1.182,Z=2.2898,P＜0.05,OR=3.261）.此外,在显性遗传模式下,SLE患者人群的G-C-G单倍型频率高于对照组（0.1287 vs 0.0361）,差异有统计学意义（P＜0.05,OR=4.332）.结论 特定遗传模式下,紫外线暴露、PDCD1基因G-C-G或G-T-A单倍型以及A-C-G单倍型与紫外线暴露的交互作用可能与中国长江以南汉族人群系统性红斑狼疮的遗传易感性相关.Objective To investigate the relationship of gene polymorphisms of programmed cell death 1 gene （PDCD1） and ultraviolet history with systemic lupus erythematosus （SLE） among the Han population in the southern region of yangtze river in China. Methods With a case-control design, a total of 159 SLE cases and 159 controls were enrolled in this study, and single nucleotide polymorphisms （SNPs） of the PDCD1 gene were determined by PCR-restrition fragment length polymorphism（RFLP）. With the aid of the logistic regression model, the effect of gene polymorphism, environmental factor and the interaction between gene and environment were fitted under the recessive, dominant, additive and codominant mode,respectively. Results Three models were screened as the optimal models under the additive mode and one model under the dominant mode, according to the lowest value of Akaike＇s Information Criteria （AIC）.After the control of age and gender, it was found that the frequency of ultraviolet exposure was higher in cases than in controls with significant difference under all models （P＜0.05）. For the haplotypes composed of the alleles of PD1.2, PD1.5 and PD1.6, there was significantly higher frequency of G-T-A haplotype （0. 1196 vs 0.0363） and lower frequency of A-C-A haplotype （0.4746 vs 0.5399） in cases than that in controls （P＜0.05） under the additive mode, and the G-T-A haplotype was associated with an increased risk for SLE （OR=4.319）, while A-C-A haplotype was shown as a protective factor for SLE （OR=0.571）.Moreover, interaction between A-C-G haplotype and ultraviolet exposure, which was related to an increased risk for SLE （β5 =1.182, Z=2.2898, P＜0.05, OR=3.261）, was also found under this mode.Additionally, the frequency of G-C-G haplotype was higher in cases than that in controls （0.1287 vs 0.0361） under the dominant mode with statistically significant difference （P ＜0.05, OR=4.332）.Conclusion Authors＇ results indicate that ultraviolet exposure, G-T-A or G

关 键 词：系统性红斑狼疮 程序性细胞凋亡1基因 单倍型 紫外线 

分 类 号：R593.241[医药卫生—内科学]