Ma Y, Ooi T C, Liu M S, Zhang H, McPherson R, Edwards A L, Forsythe I J, Frohlich J, Brunzell J D, Hayden M R
Department of Medicine, University of British Columbia, Vancouver, Canada.
J Lipid Res. 1994 Jun;35(6):1066-75.
Partial deficiency in lipolysis usually results in only mild disturbances of lipid levels. However, when this is associated with impairment of the uptake of remnant particles and increased production of triglyceride-rich lipoproteins stimulated by environmental factors such as during normal pregnancy, chylomicronemia may ensue. We have previously reported a patient who had approximately 12% of normal LPL activity and developed severe chylomicronemia during pregnancy (Ma et al. 1993. J. Clin. Invest. 91: 1953-1958). Here we report four new patients with pregnancy-induced chylomicronemia. In the nonpregnant state, these patients had mild to modest elevation of triglyceride levels ranging from 80 to 623 mg/dl (0.9-7.0 mmol/l) but during the third trimester they became severely chylomicronemic with triglyceride levels ranging from 2314 to 14,596 mg/dl (26 to 164 mmol/l). Three of these four patients had partial lipoprotein lipase (LPL) deficiency. The molecular characterization of the LPL gene in these three patients with partial LPL deficiency revealed four novel unpublished mutations. Patient #1 is a compound heterozygote for Leu252Arg and Ala261Thr mutations which are associated with 25% of normal LPL activity. In addition, she has an apoE3/2 genotype. Patient #2 is a heterozygote for a Asn291Ser substitution with 69% of LPL activity and also has an apoE3/2 genotype, while patient #3 is a heterozygote for a Trp382Stop mutation with 54% of normal LPL activity and has an apoE4/2 genotype. The fourth patient (#4) with pregnancy-induced chylomicronemia does not have LPL deficiency and has an apoE3/3 genotype. The previously reported patient (#5) who had 12% of normal LPL activity due to homozygosity for a Ser172Cys mutation also has an E3/3 genotype. Our data suggest that mutations in the LPL gene that cause partial LPL deficiency might be a frequent factor in the pathogenesis of pregnancy-induced chylomicronemia.
脂肪分解部分缺陷通常仅导致血脂水平轻度紊乱。然而，当这与残余颗粒摄取受损以及在正常妊娠等环境因素刺激下富含甘油三酯的脂蛋白生成增加相关时，可能会发生乳糜微粒血症。我们之前报道过一名患者，其脂蛋白脂肪酶（LPL）活性约为正常水平的12%，在孕期发生了严重的乳糜微粒血症（Ma等人，1993年。《临床研究杂志》91: 1953 - 1958）。在此，我们报告4例新的妊娠诱发乳糜微粒血症患者。在非孕状态下，这些患者的甘油三酯水平轻度至中度升高，范围为80至623毫克/分升（0.9 - 7.0毫摩尔/升），但在孕晚期，他们出现严重的乳糜微粒血症，甘油三酯水平范围为2314至14,596毫克/分升（26至164毫摩尔/升）。这4例患者中有3例存在部分脂蛋白脂肪酶（LPL）缺陷。对这3例部分LPL缺陷患者的LPL基因进行分子特征分析，发现了4个新的未发表的突变。患者1是Leu252Arg和Ala261Thr突变的复合杂合子，这些突变与25%的正常LPL活性相关。此外，她具有apoE3/2基因型。患者2是Asn291Ser替代的杂合子，LPL活性为69%，也具有apoE3/2基因型，而患者3是Trp382Stop突变的杂合子，LPL活性为正常水平的54%，具有apoE4/2基因型。第4例妊娠诱发乳糜微粒血症患者（患者4）不存在LPL缺陷，具有apoE3/3基因型。之前报道的患者（患者5）由于Ser172Cys突变纯合导致LPL活性为正常水平的12%，也具有E3/3基因型。我们的数据表明，导致部分LPL缺陷的LPL基因突变可能是妊娠诱发乳糜微粒血症发病机制中的常见因素。
