基于核心家系的XRCC1基因多态性与鼻咽癌易感性的关联分析

目的 利用以核心家系为基础的关联研究探讨X射线修复交叉互补基因1(XRCC1)多态性与鼻咽癌易感性之间的关系.方法 收集457个广东鼻咽癌核心家系(包含2134名成员)作为研究对象.每一个家系由父母和至少有1名患鼻咽癌的子女构成.采用聚合酶链反应-限制性片段长度多态性方法对XRCC1基因中3个单核苷酸多态性(SNP)位点(其参考SNP编号分别为rs1799782、rs25489和rs25487)进行基因分型.运用家系为基础的相关性检验(family-based association test,FBAT)软件分析这3个SNP位点基因型及单体型与鼻咽癌易感性之间的关联性.结果 FBAT 分析结果显示:XRCC1基因的3个SNP位点基因型及单体型与鼻咽癌的易感性之间无显著相关性(rs1799782:x2=1.006,P=0.605;rs25489:x2=0.470,P=0.790;rs25487:x2=2.563,P=0.278;单体型:x2=3.004,P=0.557;全局统计).基于显性或隐性模式下,rs25487位点等位基因G或A从亲代传递给子代具有增加或减少的传递(Z=1.985/-1.985,P=0.047);然而,全局统计以及基于累加模式下并没有观察到传递的增加或减少.结论 以家系为基础的相关性研究没有发现XRCC1基因多态性与鼻咽癌的易感性之间具有显著相关性.     

细胞色素P450 CYP1A1基因多态与鼻咽癌易感性的关联分析

Objective To investigate the association between CYP1A1 gene polymorphisms and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families through family-based association study. Methods A total of 457 Cantonese nuclear families, consisting of 2134 members, were recruited as subjects. Each family included two parents and at least one offspring with nasopharyngeal carcinoma. Two single nucleotide polymorphisms (SNP) in CYP1A1 named m1 (rs4646903) and m2 (rs1048943) , were genotyped by PCR-RFLP assay and verified by directly sequencing. The genotype data were analyzed with family-based association test (FBAT) software to check the linkage and association between the two genetic markers and susceptibility of nasopharyngeal carcinoma. Results FBAT analysis showed that the minor allele frequencies (MAF) of the two SN P were 0. 442 (C) and 0. 339 (G) respectively. For m1 polymorphism in CYP1A1 gene was not significantly associated with nasopharyngeal carcinoma in our study population whether stratified with VCA-IgA or not (without stratification : X2=2. 399, P=0. 301 ; with stratification : Iow-titer group (VCA-IgA<1 : 80), MAF=0. 457 (C), X2=1.221, P=0.543 ; high-titer group (VCA-IgA ≥1 : 80), MAF=0. 427 (C), X2=2. 832, P=0. 243). For m2 polymorphism, when VCA-IgA<1 : 80, the G allele showed decreased transmission under additive and dominant model (MAF=0. 347 (G) ; Zadditive=-2. 120,Padditive=0. 034;Zdominant=-2. 303,Pdominant=0.021)and a boundary P value was got with global statistic (X2=5. 394, P=0. 067). Haplotype TG (0. 057), constructed by ml and m2, might decrease nasophargneal carcinoma risk (Z=-2. 002,P=0. 045). A boundary P value was also got with global statistic (X2=7. 067 ,P=0. 070). Conclusion There was no statistical significance between ml polymorphism and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families. And this study showed that m2 polymorphism might associated with the decrease of nasopharyngeal carcinoma in Cantonese nuclear families.     

细胞色素P450 CYP1A1基因多态与鼻咽癌易感性的关联分析

Objective To investigate the association between CYP1A1 gene polymorphisms and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families through family-based association study. Methods A total of 457 Cantonese nuclear families, consisting of 2134 members, were recruited as subjects. Each family included two parents and at least one offspring with nasopharyngeal carcinoma. Two single nucleotide polymorphisms (SNP) in CYP1A1 named m1 (rs4646903) and m2 (rs1048943) , were genotyped by PCR-RFLP assay and verified by directly sequencing. The genotype data were analyzed with family-based association test (FBAT) software to check the linkage and association between the two genetic markers and susceptibility of nasopharyngeal carcinoma. Results FBAT analysis showed that the minor allele frequencies (MAF) of the two SN P were 0. 442 (C) and 0. 339 (G) respectively. For m1 polymorphism in CYP1A1 gene was not significantly associated with nasopharyngeal carcinoma in our study population whether stratified with VCA-IgA or not (without stratification : X2=2. 399, P=0. 301 ; with stratification : Iow-titer group (VCA-IgA<1 : 80), MAF=0. 457 (C), X2=1.221, P=0.543 ; high-titer group (VCA-IgA ≥1 : 80), MAF=0. 427 (C), X2=2. 832, P=0. 243). For m2 polymorphism, when VCA-IgA<1 : 80, the G allele showed decreased transmission under additive and dominant model (MAF=0. 347 (G) ; Zadditive=-2. 120,Padditive=0. 034;Zdominant=-2. 303,Pdominant=0.021)and a boundary P value was got with global statistic (X2=5. 394, P=0. 067). Haplotype TG (0. 057), constructed by ml and m2, might decrease nasophargneal carcinoma risk (Z=-2. 002,P=0. 045). A boundary P value was also got with global statistic (X2=7. 067 ,P=0. 070). Conclusion There was no statistical significance between ml polymorphism and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families. And this study showed that m2 polymorphism might associated with the decrease of nasopharyngeal carcinoma in Cantonese nuclear families.     

细胞色素P450 CYP1A1基因多态与鼻咽癌易感性的关联分析

Objective To investigate the association between CYP1A1 gene polymorphisms and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families through family-based association study. Methods A total of 457 Cantonese nuclear families, consisting of 2134 members, were recruited as subjects. Each family included two parents and at least one offspring with nasopharyngeal carcinoma. Two single nucleotide polymorphisms (SNP) in CYP1A1 named m1 (rs4646903) and m2 (rs1048943) , were genotyped by PCR-RFLP assay and verified by directly sequencing. The genotype data were analyzed with family-based association test (FBAT) software to check the linkage and association between the two genetic markers and susceptibility of nasopharyngeal carcinoma. Results FBAT analysis showed that the minor allele frequencies (MAF) of the two SN P were 0. 442 (C) and 0. 339 (G) respectively. For m1 polymorphism in CYP1A1 gene was not significantly associated with nasopharyngeal carcinoma in our study population whether stratified with VCA-IgA or not (without stratification : X2=2. 399, P=0. 301 ; with stratification : Iow-titer group (VCA-IgA<1 : 80), MAF=0. 457 (C), X2=1.221, P=0.543 ; high-titer group (VCA-IgA ≥1 : 80), MAF=0. 427 (C), X2=2. 832, P=0. 243). For m2 polymorphism, when VCA-IgA<1 : 80, the G allele showed decreased transmission under additive and dominant model (MAF=0. 347 (G) ; Zadditive=-2. 120,Padditive=0. 034;Zdominant=-2. 303,Pdominant=0.021)and a boundary P value was got with global statistic (X2=5. 394, P=0. 067). Haplotype TG (0. 057), constructed by ml and m2, might decrease nasophargneal carcinoma risk (Z=-2. 002,P=0. 045). A boundary P value was also got with global statistic (X2=7. 067 ,P=0. 070). Conclusion There was no statistical significance between ml polymorphism and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families. And this study showed that m2 polymorphism might associated with the decrease of nasopharyngeal carcinoma in Cantonese nuclear families.     

细胞色素P450 CYP1A1基因多态与鼻咽癌易感性的关联分析

Objective To investigate the association between CYP1A1 gene polymorphisms and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families through family-based association study. Methods A total of 457 Cantonese nuclear families, consisting of 2134 members, were recruited as subjects. Each family included two parents and at least one offspring with nasopharyngeal carcinoma. Two single nucleotide polymorphisms (SNP) in CYP1A1 named m1 (rs4646903) and m2 (rs1048943) , were genotyped by PCR-RFLP assay and verified by directly sequencing. The genotype data were analyzed with family-based association test (FBAT) software to check the linkage and association between the two genetic markers and susceptibility of nasopharyngeal carcinoma. Results FBAT analysis showed that the minor allele frequencies (MAF) of the two SN P were 0. 442 (C) and 0. 339 (G) respectively. For m1 polymorphism in CYP1A1 gene was not significantly associated with nasopharyngeal carcinoma in our study population whether stratified with VCA-IgA or not (without stratification : X2=2. 399, P=0. 301 ; with stratification : Iow-titer group (VCA-IgA<1 : 80), MAF=0. 457 (C), X2=1.221, P=0.543 ; high-titer group (VCA-IgA ≥1 : 80), MAF=0. 427 (C), X2=2. 832, P=0. 243). For m2 polymorphism, when VCA-IgA<1 : 80, the G allele showed decreased transmission under additive and dominant model (MAF=0. 347 (G) ; Zadditive=-2. 120,Padditive=0. 034;Zdominant=-2. 303,Pdominant=0.021)and a boundary P value was got with global statistic (X2=5. 394, P=0. 067). Haplotype TG (0. 057), constructed by ml and m2, might decrease nasophargneal carcinoma risk (Z=-2. 002,P=0. 045). A boundary P value was also got with global statistic (X2=7. 067 ,P=0. 070). Conclusion There was no statistical significance between ml polymorphism and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families. And this study showed that m2 polymorphism might associated with the decrease of nasopharyngeal carcinoma in Cantonese nuclear families.     

细胞色素P450 CYP1A1基因多态与鼻咽癌易感性的关联分析

Objective To investigate the association between CYP1A1 gene polymorphisms and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families through family-based association study. Methods A total of 457 Cantonese nuclear families, consisting of 2134 members, were recruited as subjects. Each family included two parents and at least one offspring with nasopharyngeal carcinoma. Two single nucleotide polymorphisms (SNP) in CYP1A1 named m1 (rs4646903) and m2 (rs1048943) , were genotyped by PCR-RFLP assay and verified by directly sequencing. The genotype data were analyzed with family-based association test (FBAT) software to check the linkage and association between the two genetic markers and susceptibility of nasopharyngeal carcinoma. Results FBAT analysis showed that the minor allele frequencies (MAF) of the two SN P were 0. 442 (C) and 0. 339 (G) respectively. For m1 polymorphism in CYP1A1 gene was not significantly associated with nasopharyngeal carcinoma in our study population whether stratified with VCA-IgA or not (without stratification : X2=2. 399, P=0. 301 ; with stratification : Iow-titer group (VCA-IgA<1 : 80), MAF=0. 457 (C), X2=1.221, P=0.543 ; high-titer group (VCA-IgA ≥1 : 80), MAF=0. 427 (C), X2=2. 832, P=0. 243). For m2 polymorphism, when VCA-IgA<1 : 80, the G allele showed decreased transmission under additive and dominant model (MAF=0. 347 (G) ; Zadditive=-2. 120,Padditive=0. 034;Zdominant=-2. 303,Pdominant=0.021)and a boundary P value was got with global statistic (X2=5. 394, P=0. 067). Haplotype TG (0. 057), constructed by ml and m2, might decrease nasophargneal carcinoma risk (Z=-2. 002,P=0. 045). A boundary P value was also got with global statistic (X2=7. 067 ,P=0. 070). Conclusion There was no statistical significance between ml polymorphism and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families. And this study showed that m2 polymorphism might associated with the decrease of nasopharyngeal carcinoma in Cantonese nuclear families.     

细胞色素P450 CYP1A1基因多态与鼻咽癌易感性的关联分析

Objective To investigate the association between CYP1A1 gene polymorphisms and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families through family-based association study. Methods A total of 457 Cantonese nuclear families, consisting of 2134 members, were recruited as subjects. Each family included two parents and at least one offspring with nasopharyngeal carcinoma. Two single nucleotide polymorphisms (SNP) in CYP1A1 named m1 (rs4646903) and m2 (rs1048943) , were genotyped by PCR-RFLP assay and verified by directly sequencing. The genotype data were analyzed with family-based association test (FBAT) software to check the linkage and association between the two genetic markers and susceptibility of nasopharyngeal carcinoma. Results FBAT analysis showed that the minor allele frequencies (MAF) of the two SN P were 0. 442 (C) and 0. 339 (G) respectively. For m1 polymorphism in CYP1A1 gene was not significantly associated with nasopharyngeal carcinoma in our study population whether stratified with VCA-IgA or not (without stratification : X2=2. 399, P=0. 301 ; with stratification : Iow-titer group (VCA-IgA<1 : 80), MAF=0. 457 (C), X2=1.221, P=0.543 ; high-titer group (VCA-IgA ≥1 : 80), MAF=0. 427 (C), X2=2. 832, P=0. 243). For m2 polymorphism, when VCA-IgA<1 : 80, the G allele showed decreased transmission under additive and dominant model (MAF=0. 347 (G) ; Zadditive=-2. 120,Padditive=0. 034;Zdominant=-2. 303,Pdominant=0.021)and a boundary P value was got with global statistic (X2=5. 394, P=0. 067). Haplotype TG (0. 057), constructed by ml and m2, might decrease nasophargneal carcinoma risk (Z=-2. 002,P=0. 045). A boundary P value was also got with global statistic (X2=7. 067 ,P=0. 070). Conclusion There was no statistical significance between ml polymorphism and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families. And this study showed that m2 polymorphism might associated with the decrease of nasopharyngeal carcinoma in Cantonese nuclear families.     

细胞色素P450 CYP1A1基因多态与鼻咽癌易感性的关联分析

Objective To investigate the association between CYP1A1 gene polymorphisms and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families through family-based association study. Methods A total of 457 Cantonese nuclear families, consisting of 2134 members, were recruited as subjects. Each family included two parents and at least one offspring with nasopharyngeal carcinoma. Two single nucleotide polymorphisms (SNP) in CYP1A1 named m1 (rs4646903) and m2 (rs1048943) , were genotyped by PCR-RFLP assay and verified by directly sequencing. The genotype data were analyzed with family-based association test (FBAT) software to check the linkage and association between the two genetic markers and susceptibility of nasopharyngeal carcinoma. Results FBAT analysis showed that the minor allele frequencies (MAF) of the two SN P were 0. 442 (C) and 0. 339 (G) respectively. For m1 polymorphism in CYP1A1 gene was not significantly associated with nasopharyngeal carcinoma in our study population whether stratified with VCA-IgA or not (without stratification : X2=2. 399, P=0. 301 ; with stratification : Iow-titer group (VCA-IgA<1 : 80), MAF=0. 457 (C), X2=1.221, P=0.543 ; high-titer group (VCA-IgA ≥1 : 80), MAF=0. 427 (C), X2=2. 832, P=0. 243). For m2 polymorphism, when VCA-IgA<1 : 80, the G allele showed decreased transmission under additive and dominant model (MAF=0. 347 (G) ; Zadditive=-2. 120,Padditive=0. 034;Zdominant=-2. 303,Pdominant=0.021)and a boundary P value was got with global statistic (X2=5. 394, P=0. 067). Haplotype TG (0. 057), constructed by ml and m2, might decrease nasophargneal carcinoma risk (Z=-2. 002,P=0. 045). A boundary P value was also got with global statistic (X2=7. 067 ,P=0. 070). Conclusion There was no statistical significance between ml polymorphism and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families. And this study showed that m2 polymorphism might associated with the decrease of nasopharyngeal carcinoma in Cantonese nuclear families.     

细胞色素P450 CYP1A1基因多态与鼻咽癌易感性的关联分析

Objective To investigate the association between CYP1A1 gene polymorphisms and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families through family-based association study. Methods A total of 457 Cantonese nuclear families, consisting of 2134 members, were recruited as subjects. Each family included two parents and at least one offspring with nasopharyngeal carcinoma. Two single nucleotide polymorphisms (SNP) in CYP1A1 named m1 (rs4646903) and m2 (rs1048943) , were genotyped by PCR-RFLP assay and verified by directly sequencing. The genotype data were analyzed with family-based association test (FBAT) software to check the linkage and association between the two genetic markers and susceptibility of nasopharyngeal carcinoma. Results FBAT analysis showed that the minor allele frequencies (MAF) of the two SN P were 0. 442 (C) and 0. 339 (G) respectively. For m1 polymorphism in CYP1A1 gene was not significantly associated with nasopharyngeal carcinoma in our study population whether stratified with VCA-IgA or not (without stratification : X2=2. 399, P=0. 301 ; with stratification : Iow-titer group (VCA-IgA<1 : 80), MAF=0. 457 (C), X2=1.221, P=0.543 ; high-titer group (VCA-IgA ≥1 : 80), MAF=0. 427 (C), X2=2. 832, P=0. 243). For m2 polymorphism, when VCA-IgA<1 : 80, the G allele showed decreased transmission under additive and dominant model (MAF=0. 347 (G) ; Zadditive=-2. 120,Padditive=0. 034;Zdominant=-2. 303,Pdominant=0.021)and a boundary P value was got with global statistic (X2=5. 394, P=0. 067). Haplotype TG (0. 057), constructed by ml and m2, might decrease nasophargneal carcinoma risk (Z=-2. 002,P=0. 045). A boundary P value was also got with global statistic (X2=7. 067 ,P=0. 070). Conclusion There was no statistical significance between ml polymorphism and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families. And this study showed that m2 polymorphism might associated with the decrease of nasopharyngeal carcinoma in Cantonese nuclear families.     

细胞色素P450 CYP1A1基因多态与鼻咽癌易感性的关联分析

Objective To investigate the association between CYP1A1 gene polymorphisms and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families through family-based association study. Methods A total of 457 Cantonese nuclear families, consisting of 2134 members, were recruited as subjects. Each family included two parents and at least one offspring with nasopharyngeal carcinoma. Two single nucleotide polymorphisms (SNP) in CYP1A1 named m1 (rs4646903) and m2 (rs1048943) , were genotyped by PCR-RFLP assay and verified by directly sequencing. The genotype data were analyzed with family-based association test (FBAT) software to check the linkage and association between the two genetic markers and susceptibility of nasopharyngeal carcinoma. Results FBAT analysis showed that the minor allele frequencies (MAF) of the two SN P were 0. 442 (C) and 0. 339 (G) respectively. For m1 polymorphism in CYP1A1 gene was not significantly associated with nasopharyngeal carcinoma in our study population whether stratified with VCA-IgA or not (without stratification : X2=2. 399, P=0. 301 ; with stratification : Iow-titer group (VCA-IgA<1 : 80), MAF=0. 457 (C), X2=1.221, P=0.543 ; high-titer group (VCA-IgA ≥1 : 80), MAF=0. 427 (C), X2=2. 832, P=0. 243). For m2 polymorphism, when VCA-IgA<1 : 80, the G allele showed decreased transmission under additive and dominant model (MAF=0. 347 (G) ; Zadditive=-2. 120,Padditive=0. 034;Zdominant=-2. 303,Pdominant=0.021)and a boundary P value was got with global statistic (X2=5. 394, P=0. 067). Haplotype TG (0. 057), constructed by ml and m2, might decrease nasophargneal carcinoma risk (Z=-2. 002,P=0. 045). A boundary P value was also got with global statistic (X2=7. 067 ,P=0. 070). Conclusion There was no statistical significance between ml polymorphism and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families. And this study showed that m2 polymorphism might associated with the decrease of nasopharyngeal carcinoma in Cantonese nuclear families.     

血清学指标CK19-2G2、CyFra21-1及EBVVCA-IgA/EA-IgA与鼻咽鳞癌诊断和近期疗效的价值分析

目的观察鼻咽癌患者血清中细胞角蛋白片段CK19-2G2、CyFra21-1浓度及EB病毒抗体VCA-IgA、EA-IgA滴度水平,评价以上四项肿瘤标志物对鼻咽癌诊断和预后的应用价值。方法分别检测72例正常健康人和47例放疗前后的未分化型非角化性鼻咽癌患者血清CK19-2G2、CyFra21-1浓度和VCA-IgA/EA-IgA滴度,CK19-2G2应用北京同生时代公司的仪器及试剂盒(化学发光法)检测;CyFra21-1应用罗氏电化学发光法检测;VCA-IgA应用免疫酶法检测。结果未分化型非角化性鼻咽癌患者血清CK19-2G2、CyFra21-1和VCA-IgA/EA-IgA的阳性率分别为:32.69%、46.15%、98.08%和71.15%,健康人群以上四项指标的阳性率分别为:9.32%、9.72%、16.67%和0,P<0.01;与病理诊断的一致性检验显示以上四项指标的Kappa值分别为:0.355、0.418、0.78和0.76;四项指标与临床分期有统计学意义(χ2分别为:69.04、28.21、90.36和70.49,P<0.01);未分化型鼻咽鳞癌患者放疗前后CK19-2G2和CyFra21-1阳性率呈下降趋势。结论血清CK19-2G2、CyFra21-1水平在鼻咽鳞癌患者和健康人群中有显著性差异,EBV VCA-IgA/EA-IgA滴度检测对鼻咽癌的诊断有较高准确率;鼻咽鳞癌患者血清CK19-2G2、CyFra21-1水平与病理分期相关;血清CK19-2G2、CyFra21-1的水平可能对鼻咽鳞癌患者的预后评价有一定的价值。     

转化生长因子α基因多态性与唇腭裂关联的研究

目的 探讨中国部分地区人群非综合征型唇裂伴或不伴腭裂（nsCL/P）与转化生长因子α基因（TGFα）TaqI位点多态性之间的关系。方法 采用聚合酶链反应限制片段长度多态性分析方法，对149个nsCL／P核心家庭成员DNA标本进行TGFα Taq I突变位点的基因型检测。利用传递失衡检验和以家庭为基础的关联研究（FBAT）方法，分析TGFα Taq I突变与nsCL／P发生之间的关系。结果 未发现TGFα Taq I突变的致病晓等位基因在nsCL／P核心家庭成员中存在传递不平衡（P〉0．05）；采用FBAT分析，未发现C2等位基因及C2C1基因型与nsCL／P发病危险之间关联有统计学意义（P〉0．05）。结论 TGFα Taq I突变可能不是中国部分地区人群nsCL／P发生的易感基因。     

转化生长因子α基因多态性和父亲吸烟的交互作用与唇腭裂发生的关联研究

目的探讨中国部分地区人群非综合征型唇裂伴或不伴腭裂（nsCL／P）与转化生长因子α基因（TGFα）TaqI位点多态性之间的关系,及其与父亲吸烟之间的交互作用。方法采用PCR-RFLP方法,对170个nsCL／P核心家庭成员DNA标本进行TGFα TaqI突变位点的基因型检测。利用TDT检验分析该突变与nsCL／P发生之间的关系,采用TDT检验的logistic回归模型分析TGFα基因突变与父亲吸烟之间的交互作用。结果未发现TGFα TaqI突变的致病C2等位基因在nsCL／P核心家庭成员中存在传递不平衡,但是父亲吸烟的nsCL／P核心家庭中C2C1基因型的父母将致病的C2等位基因传递给子代的频率是父亲不吸烟的nsCL／P核心家庭父母的约1／5（0．062～0．711）,控制其他环境因素后发现,父亲是否吸烟与TGFα TaqI突变位点C2等位基因传递之间是偏离乘法模型的负交互作用OR=0．102（0．017～0．619）。结论父亲是否吸烟与中国部分地区人群TGFα基因突变存在交互作用,但还有待于进一步研究加以验证。     

广西壮族人群肝癌家族聚集与细胞色素P450 2E1基因多态性等因素关系的研究

目的 探讨广西壮族人群肝癌高发家族聚集与细胞色素P450 2E1(CYP2E1)基因多态性等因素的关系.方法 在广西某肝癌高发现场壮族人群中,对10个肝癌高发家族成员(共91名)和10个无癌对照家族成员(共102名).采集外周血标本,以多聚酶链反应-限制性片段长度多态性技术(PCR-RFLP).分析所有研究对象CYP2EI基因Rsa I位点基闪型及等位基因的分布频率;并用ELISA法检测HBsAg.肝癌相关因素的暴露情况则应用统一问卷进行调查.结果 肝癌高发家族成员CYP2EI基因Rsa I位点c1/c1、c1/c2基因型频率分别为63.7%和36.3%;在对照家族成员中,相应的频率分别为48.0%和52.O%(OR=1.901,95%CI:1.067～3.387);两组成员Rsa I位点基因型分布的差异有统计学意义(X2=4.797,P=0.029).非条件logistic回归分析结果显示,当地肝癌家族聚集的主要危险因素,按其危险度由高至低排列依次为:以玉米为主食、HBsAg携带、CYP2E1 c1/c1型.结论 在广西壮族人群中,肝癌的家族聚集与家族成员的CYP2E1基因Rsa I多态性的分布,有肯定的统计学关系;CYP2E1基因Rsa I多态性的分布不是引起肝癌家族聚集的惟一因素,也不是首要因素,与其他一些因素的综合作用更为重要.     

细胞色素P450基因多态及血清硒与肺癌的关系

目的 探讨细胞色素P450(A)(CYP1A1)的MSPI基因多态性、血清硒水平单独作用以及联合作用与肺癌发生危险性的关系。方法 采用成组病例一对照研究方法，病例58例，对照62例。用PCR-RFLP技术测定CYP1A1的MsPI多态性。用双道原子荧光光度计(GHAFS)测定血清硒水平。结果 CYP1A1的MsPI基因多态性单独作用时与肺癌危险性关系无显著性差异；病例组血清硒水平显著低于对照组(P=0．001)：以血清硒水平大于等于0．109mg／L。携带CYP1A1野生型者为参照组，则血清硒水平低于0．109mg／L且携带CYPlAl突变型或杂合型或携带野生型者OR分别为9．00(P=0．006)，3．94(P=0．195)，5．40(P=0．036)，而血清硒水平大于等于0．109mg／L携带突变型或携带杂合型者OR分别为1．69(P=0．500)，1．13(P=0．705)。结论 CYP1A1基因多态性单独作用时与肺癌发生无显著相关，血清硒水平与肺癌发生呈负相关；CYP1A1基因多态性与血清硒水平联合作用时明显提高肺癌发生的危险性，在肺癌发生中存在协同作用。     

Genetic variation of infant reduced folate carrier (A80G) and risk of orofacial defects and congenital heart defects in China

PURPOSE: This study was designed to investigate whether the risks of congenital heart defects (CHD) and orofacial defects were influenced by a polymorphism of the offspring's RFC1 or by an interaction between the RFC1 gene and maternal periconceptional use of folic acid. METHODS: A case-control study was conducted. A total of 82 families with a child affected by cleft lip with or without cleft palate (CLP), 67 families with a child-affected by CHD, and 100 nonmalformed control families were genotyped using PCR-RFLP. RFC1 G allele was tested through family-based association test. RESULTS: Among mothers who did not use folic acid, the risks of 4.03 (95% CI = 1.33-12.77) for the G80/G80 genotype and 4.14 (95% CI = 1.06-16.82) for the G80/A80 genotype were observed relative to the A80/A80 genotype for CHD offspring. In family-based association tests (FBAT), offspring carrying the G allele for RFC1 is at increased risk for CHD (Z = 2.140, p < .05). No significant association was found between either RFC1 genotype or maternal folic acid supplementation and the risks of CLP. CONCLUSIONS: Our findings suggest that the RFC1 G allele is likely to be an important candidate gene in folate transport and to be associated with risk for CHD. This study found modest evidence for a gene-nutrient interaction between offspring RFC1 genotype and periconceptional intake of folic acid on the risk of congenital heart defects.     

Ordered-subset analysis (OSA) for family-based association mapping of complex traits

Association analysis provides a powerful tool for complex disease gene mapping. However, in the presence of genetic heterogeneity, the power for association analysis can be low since only a fraction of the collected families may carry a specific disease susceptibility allele. Ordered-subset analysis (OSA) is a linkage test that can be powerful in the presence of genetic heterogeneity. OSA uses trait-related covariates to identify a subset of families that provide the most evidence for linkage. A similar strategy applied to genetic association analysis would likely result in increased power to detect association. Association in the presence of linkage (APL) is a family-based association test (FBAT) for nuclear families with multiple affected siblings that properly infers missing parental genotypes when linkage is present. We propose here APL-OSA, which applies the OSA method to the APL statistic to identify a subset of families that provide the most evidence for association. A permutation procedure is used to approximate the distribution of the APL-OSA statistic under the null hypothesis that there is no relationship between the family-specific covariate and the family-specific evidence for allelic association. We performed a comprehensive simulation study to verify that APL-OSA has the correct type I error rate under the null hypothesis. This simulation study also showed that APL-OSA can increase power relative to other commonly used association tests (APL, FBAT and FBAT with covariate adjustment) in the presence of genetic heterogeneity. Finally, we applied APL-OSA to a family study of age-related macular degeneration, where cigarette smoking was used as a covariate.     

Latent class model with familial dependence to address heterogeneity in complex diseases: adapting the approach to family-based association studies

Clinical diagnoses of complex diseases may often encompass multiple genetically heterogeneous disorders. One way of dissecting this heterogeneity is to apply latent class (LC) analysis to measurements related to the diagnosis, such as detailed symptoms, to define more homogeneous disease sub-types, influenced by a smaller number of genes that will thus be more easily detectable. We have previously developed a LC model allowing dependence between the latent disease class status of relatives within families. We have also proposed a strategy to incorporate the posterior probability of class membership of each subject in parametric linkage analysis, which is not directly transferable to genetic association methods. Under the framework of family-based association tests (FBAT), we now propose to make the contribution of an affected subject to the FBAT statistic proportional to his or her posterior class membership probability. Simulations showed a modest but robust power advantage compared to simply assigning each subject to his or her most probable class, and important power gains over the analysis of the disease diagnosis without LC modeling under certain scenarios. The use of LC analysis with FBAT is illustrated using autism spectrum disorder (ASD) symptoms on families from the Autism Genetics Research Exchange, where we examined eight regions previously associated to autism in this sample. The analysis using the posterior probability of membership to an LC detected an association in the JARID2 gene as significant as that for ASD (P = 3 × 10(-5)) but with a larger effect size (odds ratio = 2.17 vs. 1.55).     

广西壮族人群肝癌家族聚集与细胞色素基因多态性等因素关系的研究

探讨广西壮族人群肝癌高发家族聚集与细胞色素P4502E1(CYP2E1)基因多态性等因素的关系。方法在广西某肝癌高发现场壮族人群中,对10个肝癌高发家族成员(共91名)和10个无癌对照家族成员(共102名)。     

Family-based tests for associating haplotypes with general phenotype data: application to asthma genetics

We provide a general purpose family-based testing strategy for associating disease phenotypes with haplotypes when phase may be ambiguous and parental genotype data may be missing. These tests for linkage and association can be used in candidate gene studies with tightly linked markers. Our proposed weighted conditional approach extends the method described in Rabinowitz and Laird to multiple markers. It is attractive because it provides haplotype tests for family-based studies that are efficient and robust to population admixture, phenotype distribution specification, and ascertainment based on phenotypes. It can handle missing parental genotypes and/or missing phase in both offspring and parents. It yields either haplotype-specific (univariate) tests or multi-haplotype (global) tests. This extension has been implemented in the freely available software haplotype FBAT. We used the haplotype FBAT program to test for associations between asthma phenotypes and single nucleotide polymorphisms (SNPs) in the beta-2 adrenergic receptor gene. Whereas no single SNP showed significant association with asthma diagnosis or bronchodilator responsiveness (quantitative trait), a haplotype-based global test found a highly significant association with asthma diagnosis (P value <0.00005) and the measure of bronchodilator responsiveness (P value =0.016).