基于家庭的TGFβ1基因-509C/T多态性与IgA肾病相关性研究  

Family-based transmission disequilibrium association study on TGFβ1 -509C/T polymorphism and IgA nephropathy

作　　者：薛超[1] 李幼姬[1] 李彩霞[2] 杜勇[1] 黄伟俊[3] 夏运风[1] 黎嘉能[4] Patrick H Maxwell 王一鸣[3] 

机构地区：[1]中山大学附属第一医院肾内科 [2]中山医学院医学统计教研室,广东广州510080 [3]中山医学院医学遗传学教研室,广东广州510080 [4]香港大学玛丽医院内科 [5]Department of Medicine,Hammersmith Hospital,Imperial College,London,UK

出　　处：《中国病理生理杂志》2005年第3期422-426,共5页Chinese Journal of Pathophysiology

基　　金：美国中华医学基金资助项目 (No .98- 6 77) ;国家自然科学基金资助项目 (No .30 170 4 34) ;广东省自然科学基金资助项目 (No .2 0 0 1314 0 )

摘　　要：目的 :以家庭为基础 ,利用遗传不平衡原理研究转化生长因子β1(TGFβ1)基因 - 5 0 9C/T多态性与中国汉族人群IgA肾病的相关关系。方法 :用PCR -RFLP法和PCR产物直接测序法鉴定基因型 ,采用家庭为基础的传递不平衡检验 (TDT)、单体型相对风险 (HRR)分析的方法。进一步病例追踪随访。结果 :① 10 6个满足经典TDT分析的核心家庭中 ,杂合子父母传递给患病子代的等位基因频率不比预期值高 ,16 8个家庭的扩展TDT分析也验证了这一结果 (χ2 =0 5 5 8,P >0 0 5 ;χ2 =0 399,P >0 0 5 )。② 130个满足HRR分析的核心家庭中 ,HRR分析显示TGFβ1基因 - 5 0 9C/T多态性不使病人具有更高的发病风险 (Genotype -basedHRR χ2 =0 6 77,P >0 0 5 ,Haplotype -basedHRR χ2 =0 6 5 0 ,P >0 0 5 ,HRR =0 86 5 )。③ 2 96例IgA肾病病人的追踪随访发现 :肾功能恶化组CC基因型出现频率显著增高 [χ2 (CC/others) =10 4 0 2 ,P <0 0 1,OR =2 90 0 ]。结论 :中国汉族人群中 ,TGFβ1基因 - 5 0 9C/T多态性可能和肾病的病程进展相关。但和IgA肾病的易感性不相关。AIM: To investigate the relationship between transforming groupth factor beta 1 (TGFβ1)-509C/T polymorphism and IgA nephropathy using family-based analysis of transmission disequilibrium test and haplotype relative risk. METHODS: The genotypes of TGFβ1 -509C/T were determined by PCR-RFLP and direct sequencing. Two family-based designs, transmission disequilibrium test (TDT) and haplotype-based haplotype relative risk (HRR) were employed for the data analysis. The patients were followed up and clinical data retrieved and compared. RESULTS: ① No transmission disequilibrium was found from heterozygous parents onto patients in our 106 trios analyzed by TDT ( χ 2=0 559, P >0 05). ② No increased risks of contracting the disease oweing to-509C/T polymorphism of TGFβ1 in our 130 trios analyzed by either genotype-based HRR or haplotype-based HRR ( χ 2=0 667, P>0 05; χ 2=0 650, P>0 05 , HRR=0 878). ③ 296 cases of IgA nephropathy were tracked for nearly two years, the results showed that the CC genotype frequency was very significantly higher in patients with renal function deterioration χ 2 (CC/others)=10 402, P <0 01, OR=2 900]. CONCLUSION: TGFβ1-509 CC genotype may be associated with progression of IgA nephropathy, but the -509C/T polymorphism is not associated with susceptibility to this disease in Chinese Han population.

关 键 词：肾小球肾炎 IgA 转化生长因子Β 多态现象(遗传学) 

分 类 号：R363[医药卫生—病理学]