LPL基因旁侧区域内多态性与高血压病或血压数量性状的连锁分析

Linkage analysis of polymorphisms near the lipoprotein lipase gene with hypertension or blood pressure in Chinese

目的 绝大多数高血压病患者都伴有血脂代谢异常 ,而且高血压在具有家族性混合型高脂血症的家庭中发生频率更高。由此认为 ,血压调节和血脂代谢可能存在共同的遗传基础。本研究旨在探讨脂蛋白脂酶 (LPL)基因是否为国人高血压病发生的易感基因。方法 筛选了 1 4 8个高血压病家系 ,使用ABITM377测序仪 ,结合GENESCAN技术对LPL基因旁侧区域内 7个多态性进行基因型检测。使用S .A .G .E/SIBPAL2和SOLAR程序完成血压质量和数量性状的弱参数连锁分析 ,使用TDT/STDT进行连锁不平衡分析。所有分析均对年龄、性别和体重指数进行了校正。结果 (1 )使用SOLAR程序 ,连锁分析提示D8S2 6 1与收缩压连锁 (LOD =2 5 2 )。使用LOD值拟合分析 (1 00 0 0次 ) ,进一步证实D8S2 6 1与收缩压连锁 (P =0 0 0 0 1 )。 (2 )使用S .A G E/SIBPAL2程序观察到D8S1 1 4 5 (P =0 0 0 97)、D8S5 1 1 (P =0 0 0 36 )和D8S5 6 0 (P =0 0 1 1 5 )与高血压连锁 ;D8S2 6 1和NEFL分别与收缩压和舒张压均连锁。 (3)TDT/STDT分析提示D8S2 6 1的第三等位基因与高血压存在连锁不平衡 (χ2 =8 6 4 3,P <0 0 1 ;Z′ =2 4 0 8,P <0 0 5 ) ,Bonferroni校正值Z′ =3 5 1 7,P <0 0 1。

Objective To explore whether lipoprotein lipase (LPL) gene or genes nearby are linked with or associated with susceptibitily to essential hypertension (EH) in Chinese population. Methods Seven polymorphismsnear the LPL gene were analyzed with ABI TM377 sequencer combined with fluorescencebased gene scan in 148 hypertensive families. Linkage analyses were performed by S.A.G.E/SIBPAL2 and SOLAR programs, and transmission/disequilibrium test was conducted by TDT/STDT program. All analyses were adjusted for age, sex and body mass index (BMI). Results (1) A linkage between D8S261 and SBP was identified, with a LOD score of 2.52, and that was confirmed by conducting permutation (10 000 replicates)(P=0.0001). (2) Using S.A.G.E/SIBPAL2 program, evidence for linkage between EH and the markers D8S1145, D8S511 and D8S560 was observed respectively. D8S261 and NEFL were linked with SBP and DBP respectively. (3)TDT/STDT analysis also suggested a significant linkagedisequilibrium between the allele 3 of D8S261 and EH (χ 2 =8.643, P<0.01; Z′=2.408,P<0.05) with Bonferroni′ s corrected value Z′=3.517, P<0.01. Conclusion Our data suggested that the genes near the region of the LPL gene or LPL gene itself might contribute to the individual blood pressure variation in Chinese.