de Bruin T W, Mailly F, van Barlingen H H, Fisher R, Castro Cabezas M, Talmud P, Dallinga-Thie G M, Humphries S E
Department of Medicine, Academic Hospital Utrecht, The Netherlands.
Eur J Clin Invest. 1996 Aug;26(8):631-9. doi: 10.1111/j.1365-2362.1996.tb02146.x.
The role of the lipoprotein lipase (LPL) gene in familial combined hyperlipidaemia (FCH) is unclear at present. We screened a group of 28 probands with familial combined hyperlipidaemia and a group of 91 population controls for two LPL gene mutations, D9N and N291S. LPL-D9N was found in two probands and one normolipidaemic population control. LPL-N291S was found in four probands and four population controls. Subsequently, two pedigrees from probands with the D9N mutation and two pedigrees from probands with the N291S mutation were studied, representing a total of 24 subjects. Both LPL gene mutations were associated with a significant effect on plasma lipids and apolipoproteins. Presence of the D9N mutation (n = 7) was associated with hypertriglyceridaemia [2.69 +/- 1.43 (SD) mmol L-1] and reduced plasma high-density lipoprotein cholesterol (HDL-C) concentrations (0.92 +/- 0.21 mmol L-1) compared with 11 non-carriers (triglyceride 1.75 +/- 0.64 mmol L-1; HDL-C 1.23 +/- 0.30 mmol L-1, P = 0.03 and P = 0.025 respectively). LPL-D9N carriers had higher diastolic blood pressures than non-carriers. LPL-N291S carriers (n = 6) showed significantly higher (26%) apo B plasma concentrations (174 +/- 26 mg dL-1) than non-carriers (138 +/- 26 mg dL-1; P = 0.023), with normal post-heparin plasma LPL activities. Linkage analysis revealed no significant relationship between the D9N or N291S LPL gene mutations and the FCH phenotype (hypertriglyceridaemia, hypercholesterolaemia or increased apo B concentrations). It is concluded that the LPL gene did not represent the major single gene causing familial combined hyperlipidaemia in the four pedigrees studied, but that the LPL-D9N and LPL-N291S mutations had significant additional effects on lipid and apolipoprotein phenotype.
脂蛋白脂肪酶（LPL）基因在家族性混合型高脂血症（FCH）中的作用目前尚不清楚。我们对一组28名家族性混合型高脂血症先证者和一组91名正常人群对照进行筛查，检测两种LPL基因突变，即D9N和N291S。在两名先证者和一名血脂正常的人群对照中发现了LPL-D9N。在四名先证者和四名人群对照中发现了LPL-N291S。随后，对来自携带D9N突变先证者的两个家系以及来自携带N291S突变先证者的两个家系进行了研究，共涉及24名受试者。两种LPL基因突变均对血浆脂质和载脂蛋白有显著影响。与11名非携带者相比，携带D9N突变者（n = 7）出现高甘油三酯血症[2.69±1.43（标准差）mmol/L-1]，血浆高密度脂蛋白胆固醇（HDL-C）浓度降低（0.92±0.21 mmol/L-1）（甘油三酯1.75±0.64 mmol/L-1；HDL-C 1.23±0.30 mmol/L-1，P值分别为0.03和0.025）。LPL-D9N携带者的舒张压高于非携带者。LPL-N291S携带者（n = 6）的载脂蛋白B血浆浓度显著高于非携带者（高26%）（174±26 mg/dL-1），而肝素后血浆LPL活性正常。连锁分析显示，D9N或N291S LPL基因突变与FCH表型（高甘油三酯血症、高胆固醇血症或载脂蛋白B浓度升高）之间无显著关系。结论认为，在所研究的四个家系中，LPL基因并非导致家族性混合型高脂血症的主要单基因，但LPL-D9N和LPL-N291S突变对脂质和载脂蛋白表型有显著的附加影响。
