Heiba I M, DeMeester C A, Xia Y R, Diep A, George V T, Amos C I, Srinivasan S R, Berenson G S, Elston R C, Lusis A J
Department of Biometry and Genetics, LSU Medical Center, New Orleans 70112-1393.
Am J Med Genet. 1993 Nov 1;47(6):875-83. doi: 10.1002/ajmg.1320470615.
A pedigree of a large family with high prevalence of heart disease is subjected to association and sib-pair linkage analysis to investigate the role of 5 candidate genes in the regulation of lipoprotein metabolism and the development of coronary artery disease. At the 5% nominal significance level, the apolipoprotein B locus (APOB) was found to be linked to high-density lipoprotein cholesterol level (HDL-C), low-density lipoprotein cholesterol level (LDL-C), the ratio HDL-C/LDL-C, and apolipoprotein AI level times this ratio (apoAI x LDL-C/HDL-C). APOB (PvuII) was strongly associated with apolipoprotein B levels (apoB) (P = 0.006) and the VNTR region of the APOB locus showed highly significant association between allele 7 and low triglyceride levels (P = 0.004). No significant linkage results were found with cholesterol ester transfer protein (CETP). At the 1% nominal significance level, CETP [TaqI(B)] showed significant association with LDL-C, apoB, and HDL-C/LDL-C. There was significant linkage of lipoprotein lipase (LPL) with very-low-density lipoprotein cholesterol and the ratio apoAI/HDL-C, and strong association results between LPL (HindIII) and triglyceride levels (P = 0.005). At the 5% nominal significance level, haptoglobin (HPA) was associated with HDL-C, HDL-C/LDL-C, apoAI/HDL-C and apoAI x LDL-C/HDL-C. The apolipoprotein AI locus did not show any significant linkages or associations. The study thus indicated that genetic variation of APOB, LPL, CETP, and lecithin cholesterol acyl transferase (which is linked to HPA and CETP) may play an important role in the regulation of lipoprotein metabolism and could contribute to the risk of coronary artery disease.
对一个心脏病高患病率的大家庭进行家系关联分析和同胞对连锁分析，以研究5个候选基因在脂蛋白代谢调节和冠状动脉疾病发生发展中的作用。在5%的名义显著性水平下，发现载脂蛋白B基因座（APOB）与高密度脂蛋白胆固醇水平（HDL-C）、低密度脂蛋白胆固醇水平（LDL-C）、HDL-C/LDL-C比值以及载脂蛋白AI水平乘以该比值（apoAI×LDL-C/HDL-C）相关联。APOB（PvuII）与载脂蛋白B水平（apoB）密切相关（P = 0.006），并且APOB基因座的可变数目串联重复序列（VNTR）区域显示等位基因7与低甘油三酯水平之间存在高度显著关联（P = 0.004）。未发现胆固醇酯转运蛋白（CETP）有显著的连锁结果。在1%的名义显著性水平下，CETP [TaqI(B)]与LDL-C、apoB和HDL-C/LDL-C存在显著关联。脂蛋白脂肪酶（LPL）与极低密度脂蛋白胆固醇以及apoAI/HDL-C比值存在显著连锁，并且LPL（HindIII）与甘油三酯水平之间有强关联结果（P = 0.005）。在5%的名义显著性水平下，触珠蛋白（HPA）与HDL-C、HDL-C/LDL-C、apoAI/HDL-C以及apoAI×LDL-C/HDL-C相关联。载脂蛋白AI基因座未显示任何显著的连锁或关联。该研究因此表明，APOB、LPL、CETP以及与HPA和CETP相关的卵磷脂胆固醇酰基转移酶的基因变异可能在脂蛋白代谢调节中起重要作用，并可能导致冠状动脉疾病风险增加。
