基因多态性与疾病关联研究中Hardy-Weinberg平衡的影响因素分析

目的 根据炎性基因多态性与胃癌易感性家系比较研究的数据,分析基因多态性与疾病关联研究中Hardy-Weinberg(H-W)平衡的影响因素,揭示群体中等位基因频率在逐代传递中平衡偏离的原因.方法 对胃癌风险因素的各种基因型的状态进行H-W平衡检验、连锁不平衡分析、Cochran-Armitage趋势检验和分析.结果 (1)单位点IL-1B-31、IL-1B-511、IL-1RN和TNF-A-308的病例组和对照组均显著背离H-W平衡(P<0.01),MIF-173趋于平衡.(2)双位点统计分析,各位点组合的H-W χT2检验均偏离表型组合概率的期望值(P<0.01).(3)Cochran-Armitage趋势检验不同组IL-1B-511和IL-1RN位点分布的差异有统计学意义(P<0.05),表明群体中可能存在群体分层.结论 (1)受连锁不平衡相结合的频率依赖性选择、突变及其共同作用的影响,IL-1B-31、IL-1B-511、IL-IRN和TNF-A-308位点的基因型频率在群体中分布偏离H-W平衡.(2)双位点遗传平衡检验模式更能反映表型组合适合度的差异.(3)群体分层是H-W平衡偏离的另一影响因素.

Influential factors of Hardy-Weinberg equilibrium on the study of association between gene polymorphism and disease

Objective According to the data collected from gastric cancer families comparative study, the influence factors of Hardy-Weinberg (H-W) equilibrium in the association studies of gene polymorphism and disease were analyzed to reveal the reasons that affecting the equilibrium deviation in the group. Methods Varieties of risk genotype for gastric cancer were analyzed and detected with H-W equilibrium, genetic linkage disequilibrium analysis and Cochran-Armitage trend test. Results (1) Significant deviations from H-W equilibrium were observed in IL-1B-31, IL-IB-511, IL-IRN and TNF-A-308 of the cases and controls (P<0.01). MIF-173 tended to be equilibrium in the population. (2)Deviations from expectations of phenotypes combination probability were observed in two-site H-W χ2 tests (P< 0.01). (3)The Cochran-Armitage trend test showed that distribution of IL-1B-511 and IL-1RN were significantly different(P<0.05), suggesting that population stratification might have existed in the group. Conclusions (1)Affected by frequency-dependent selection, under the combination of linkage disequilibrium, mutations and interaction, genotype frequency of IL-1B-31, IL-1B-511, IL-1RN and TNF-A-308 showed deviation from H-W equilibrium in population. (2)Two-site genetic equilibrium test model seemed better to reflect the differences of phenotypic combination fitness. (3)Population stratification was another factor to express the deviation from H-W equilibrium.