细胞因子及相关受体基因位点与中国人原发性高血压的连锁分析

目的 在中国汉族人中进行细胞因子及相关受体基因位点与原发性高血压（essential hypertension,EH)的连锁分析，以筛选EH易感基因。方法 在8种细胞因子及相关受体基因附近选择DNA短串联重复序列（short tandem repeat,STR)作为遗传标记，采用荧光标记STR引物及基因分型技术，对上海地区95个汉族EH核心家系，477个成员染色体上7个遗传标记位点进行基因分型，运用GENEHUNTER软件计算最大Lod值、两点非参数连锁分析（non-parametric linkage analysis,NPL)及传递／不平衡检验（transmission/disequilibrium test,TDT)。结果 TDT显示D14S61位点等位基因在EH患病同胞中传递显著不平衡（χ^2=14.29,P=0.00016)最大Lod值为0.72;NPL的Z＝0．78，P＞0．05。其余位点最大Lod值均＜－1，TDT和NPL统计结果未提示这些位点传递不平衡与EH存在连锁（P＞0．05）。结论 D14S61位点在EH患病同胞中存在明显的传递不平衡。已知转化生长因子β3基因距该位点0.1cM，提示这一染色体区域附近基因与EH关系有待进一步研究。

Linkage analysis of cytokine and cytokine-related receptor gene loci and essential hypertension in Chinese

OBJECTIVE: To investigate the genetic linkage between several cytokine and cytokine-related receptor gene loci and essential hypertension (EH) in Chinese. METHODS: Linkage between seven genetic markers and EH in 95 Chinese nuclear families with EH (including 477 subjects) was analyzed using a technique of fluorescence-based gene scan with DNA short tandem repeat loci. These markers were selected from the chromosomal regions nearby eight cytokines and their receptor genes. The two-point non-parametric linkage analysis (NPL), maximum Lod score and transmission/disequilibrium test (TDT) with GENEHUNTER software package were used in this study. RESULTS: Result of TDT showed significant transmission disequilibrium between D14S61 and EH (Chi square 14.29,P=0.00016) although NPL and Lod score revealed no significant linkage (Z=0.78, P>0.05 and Lod score =0.72 respectively) at this locus. No linkage between other loci typed and EH was found by the three genetic analysis methods (P>0.05 or Lod score<-1). CONCLUSION: Alleles at D14S61 were of significant transmission disequilibrium in affected siblings. Transforming growth factor beta 3 is 0.1 cM away from D14S61, which suggests that the relationship between genes at or near this regions and EH needs to be further explored.