Yang Wenjie, Huang Jianfeng, Ge Dongliang, Yao Cailiang, Duan Xiufang, Gan Wenqi, Huang Guangyong, Zhao Jiangong, Hui Rutai, Shen Yan, Qiang Boqin, Gu Dongfeng
Division of Population Genetics, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P R China.
Hypertens Res. 2003 Jun;26(6):459-64. doi: 10.1291/hypres.26.459.
Essential hypertension (EH) is a common late-onset disease that exhibits complex genetic heterogeneity. Human lipoprotein lipase (LPL) is a rate-limiting enzyme that regulates the catabolism of triglycerides (TG) and chylomicrons (CM). Since dyslipidemia is a common finding in hypertensive patients, the LPL gene is a logical candidate gene that could contribute to the development of hypertension. Using linkage analysis in 148 Chinese hypertensive families, we identified a region of linkage with systolic blood pressure (SBP) and diastolic blood pressure (DBP) that consisted of a 10.6-cM interval defined by markers D8S1145, D8S261, and D8S282 on chromosome 8, which maps between 31 to 41.6 cM from the 8p-telomere contained LPL gene, with statistically significant p values for the marker D8S261 (p = 0.0021 for SBP, and p = 0.0395 for DBP). In the qualitative-trait linkage analysis, evidence for linkage between the marker D8S1145 and EH was found (p = 0.0286). The transmission/disequilibrium test (TDT/S-TDT) also supported a significant linkage-disequilibrium of the allele 3 of D8S261 with EH (chi2 = 8.643, p < 0.01). Furthermore, the marker neurofilament light polypeptide (NEFL) (11 cM centromeric to the LPL gene) appeared to be in linkage with SBP and DBP (p = 0.0329 for SBP; p = 0.0319 for DBP). Additionally, two flanking markers for LPL, D8S511 (9.5 cM telomeric to the LPL gene) and D8S560 (3.2 cM centromeric to the LPL gene), also showed significant linkage with EH (p = 0.0036 for D8S511; p = 0.0115 for D8S560). Previous knowledge about the physiological involvement of LPL in blood pressure regulation and the present findings of variation near the LPL gene support the proposition that a region near the LPL gene or the LPL gene itself might contribute to the individual blood pressure variation in Chinese.
原发性高血压（EH）是一种常见的晚发性疾病，具有复杂的遗传异质性。人脂蛋白脂肪酶（LPL）是一种调节甘油三酯（TG）和乳糜微粒（CM）分解代谢的限速酶。由于血脂异常在高血压患者中很常见，LPL基因是一个可能导致高血压发生的合理候选基因。通过对148个中国高血压家族进行连锁分析，我们确定了一个与收缩压（SBP）和舒张压（DBP）连锁的区域，该区域由位于8号染色体上的标记D8S1145、D8S261和D8S282定义的10.6厘摩区间组成，该区间位于距8p端粒31至41.6厘摩之间，包含LPL基因，标记D8S261具有统计学显著的p值（SBP的p = 0.0021，DBP的p = 0.0395）。在质量性状连锁分析中，发现标记D8S1145与EH之间存在连锁证据（p = 0.0286）。传递/不平衡检验（TDT/S - TDT）也支持D8S261的等位基因3与EH存在显著的连锁不平衡（χ2 = 8.643，p < 0.01）。此外，标记神经丝轻链多肽（NEFL）（位于LPL基因着丝粒侧11厘摩处）似乎与SBP和DBP存在连锁（SBP的p = 0.0329；DBP的p = 0.0319）。此外，LPL的两个侧翼标记，D8S511（位于LPL基因端粒侧9.5厘摩处）和D8S560（位于LPL基因着丝粒侧3.2厘摩处），也显示出与EH存在显著连锁（D8S511的p = 0.0036；D8S560的p = 0.0115）。先前关于LPL在血压调节中的生理作用的知识以及目前在LPL基因附近发现的变异支持这样的观点，即LPL基因附近的区域或LPL基因本身可能导致中国人个体血压的差异。
