Talmud P J, Hall S, Holleran S, Ramakrishnan R, Ginsberg H N, Humphries S E
Centre for Genetics of Cardiovascular Disorders, University College London Medical School, UK.
J Lipid Res. 1998 Jun;39(6):1189-96.
The lipoprotein lipase (LPL) promoter -93T/G transition has previously been reported as having a triglyceride (Tg)-lowering effect, whereas the D9N variant has been shown to have a Tg-raising effect. These two variants were studied in 66 healthy subjects of Hispanic and 42 subjects of African-American origin, who had participated in a study of postprandial lipemia. While the allele frequency of the -93G was significantly different in the Hispanics and African Americans (0.09: 95% CI 0.04-0.13 and 0.28: 95% CI 0.19-0.38; P=0.0001, respectively), the N9 allele frequency was not different (0.06: 95% CI 0.02-0.1 and 0.05: 95% CI 0.002-0.093, respectively). Linkage disequilibrium between the -93T/G and D9N was highly significant in Hispanics (delta=0.67. P=0.0001), compared to delta=0.09 (NS) in African-Americans. In the combined group, compared to individuals with the common genotype (TT/DD; n=71) with fasting plasma Tg of 1.34 (+/-4.5% SEM) mmol/l, carriers of the G/D haplotype (TG/DD + GG/DD; n=25) had significantly lower plasma Tg levels of 1.08 (+/-10% SEM) mmol/l (P < 0.02). After the fat meal, compared to individuals with neither mutation, TT/DD, the effect of the G/D haplotype was to reduce significantly postprandial Tg (P < 0.036). Retinyl palmitate concentration at 5 hrs was significantly lower in G/D carriers than TT/DD individuals (P < 0.05). The lipid-raising effect of the N9 allele in carriers of the -93G (TG/DN + GG/DN) and effect on postprandial Tg clearance was not significant in this group. Thus carriers of the G/D haplotype have lower fasting plasma Tg and reduced alimentary lipemia. This allele may be associated with reduced risk of coronary artery disease.
此前有报道称，脂蛋白脂肪酶（LPL）启动子-93T/G转换具有降低甘油三酯（Tg）的作用，而D9N变异体则具有升高Tg的作用。在66名西班牙裔健康受试者和42名非裔美国健康受试者中对这两种变异体进行了研究，这些受试者参与了一项餐后血脂异常的研究。虽然-93G的等位基因频率在西班牙裔和非裔美国人中存在显著差异（分别为0.09：95%CI 0.04 - 0.13和0.28：95%CI 0.19 - 0.38；P = 0.0001），但N9等位基因频率并无差异（分别为0.06：95%CI 0.02 - 0.1和0.05：95%CI 0.002 - 0.093）。与非裔美国人中的delta = 0.09（无显著性差异）相比，-93T/G与D9N之间的连锁不平衡在西班牙裔中高度显著（delta = 0.67，P = 0.0001）。在合并组中，与空腹血浆Tg为1.34（±4.5%标准误）mmol/l的常见基因型（TT/DD；n = 71）个体相比，G/D单倍型携带者（TG/DD + GG/DD；n = 25）的血浆Tg水平显著更低，为1.08（±10%标准误）mmol/l（P < 0.02）。进食脂肪餐后，与无突变的个体TT/DD相比（TT/DD），G/D单倍型的作用是显著降低餐后Tg（P < 0.036）。G/D携带者在5小时时的视黄醇棕榈酸酯浓度显著低于TT/DD个体（P < 0.05）。在该组中，-93G携带者（TG/DN + GG/DN）中N9等位基因的血脂升高作用及其对餐后Tg清除的影响并不显著。因此，G/D单倍型携带者的空腹血浆Tg较低且饮食性血脂异常减轻。该等位基因可能与降低冠状动脉疾病风险相关。
