目的研究DNA修复基因XRCC1(X-ray repair cross-complementing group 1)编码区Arg194Trp及Arg399Gln多态位点所构成的单倍体型在中国汉族人群中的分布,并探讨与结肠癌发生的易感风险相关性。方法所有外周血样本DNA提取后,采用PCR-RFLP(...目的研究DNA修复基因XRCC1(X-ray repair cross-complementing group 1)编码区Arg194Trp及Arg399Gln多态位点所构成的单倍体型在中国汉族人群中的分布,并探讨与结肠癌发生的易感风险相关性。方法所有外周血样本DNA提取后,采用PCR-RFLP(聚合酶链反应-限制性片段长度多态性)方法,检测207例中国汉族结肠癌患者与255例正常对照者XRCC1基因Arg194Trp及Arg399Gln的基因型,并利用PHASE1.0软件构建其单倍体型,以非条件Logistic回归校正混杂因素如性别、年龄、吸烟、饮酒等,进行单倍体型与结肠癌患者风险关联的统计学分析。结果PCR-RFLP检测结果显示XRCC1基因Arg194Trp与Arg399Gln多态性在本研究人群462例样本中均存在,XRCC1多态性位点的各自的等位基因频率分布符合Hardy-Weinberg平衡定律;Trp-Gln单倍体型在本研究中结肠癌患者与健康正常人之间有显著的统计学差异:P<0.01;OR7.23,95%CI 3.52～18.25。结论在中国汉族人群中,XRCC1基因Trp-Gln单倍体型与结肠癌的发生有着显著的易感关联。展开更多
PURPOSE: The aim of this research was to determine the molecular factors of influence on the clinical expression of Leber hereditary optic neuropathy (LHON), which might aid in counseling LHON patients and families. T...PURPOSE: The aim of this research was to determine the molecular factors of influence on the clinical expression of Leber hereditary optic neuropathy (LHON), which might aid in counseling LHON patients and families. The prevalence of LHON in the Dutch population was determined. DESIGN: Observational, retrospective population cohort study. METHODS: The clinical characteristics of LHON patients of 25 families, previously described in 1963, were reevaluated. The mutation and haplotype were determined in the DNA of one affected LHON patient per family. The genotype of their relatives could be deducted, enabling us to evaluate retrospectively the genotype-phenotype correlation. The prevalence of LHON was determined on the basis of anamnestic evaluation of patients in 1963 and by using population registers of that period. RESULTS: The LHON mutation does not influence disease penetrance (50% in male subjects; 10% to 20% in female subjects). More than half of the patients with the 14484 mutation exhibit a partial recovery of vision, regardless of the acuteness of disease onset (P=.001), whereas only 22% of the 11778 carriers and 15.4% of the 3460 carriers recovered. The recovery did not take place within the first year after onset and was uncommon after four years. The onset of LHON is in general very acute but might be more gradual in 11778 carriers and in children. The calculated prevalence of LHON in the Dutch population (1/39,000) is very likely an underestimation caused by a selection bias of familial cases in the original study. CONCLUSIONS: The LHON genotype influences the recovery of vision and disease onset but is unrelated to age, acuteness of onset, or gender. The genotype does not influence disease penetrance. Children might exhibit a slower onset of disease.展开更多
文摘PURPOSE: The aim of this research was to determine the molecular factors of influence on the clinical expression of Leber hereditary optic neuropathy (LHON), which might aid in counseling LHON patients and families. The prevalence of LHON in the Dutch population was determined. DESIGN: Observational, retrospective population cohort study. METHODS: The clinical characteristics of LHON patients of 25 families, previously described in 1963, were reevaluated. The mutation and haplotype were determined in the DNA of one affected LHON patient per family. The genotype of their relatives could be deducted, enabling us to evaluate retrospectively the genotype-phenotype correlation. The prevalence of LHON was determined on the basis of anamnestic evaluation of patients in 1963 and by using population registers of that period. RESULTS: The LHON mutation does not influence disease penetrance (50% in male subjects; 10% to 20% in female subjects). More than half of the patients with the 14484 mutation exhibit a partial recovery of vision, regardless of the acuteness of disease onset (P=.001), whereas only 22% of the 11778 carriers and 15.4% of the 3460 carriers recovered. The recovery did not take place within the first year after onset and was uncommon after four years. The onset of LHON is in general very acute but might be more gradual in 11778 carriers and in children. The calculated prevalence of LHON in the Dutch population (1/39,000) is very likely an underestimation caused by a selection bias of familial cases in the original study. CONCLUSIONS: The LHON genotype influences the recovery of vision and disease onset but is unrelated to age, acuteness of onset, or gender. The genotype does not influence disease penetrance. Children might exhibit a slower onset of disease.
