Department of Medicine (Division of Medical Genetics), University of Washington, Seattle, WA, USA.
J Lipid Res. 2010 May;51(5):983-90. doi: 10.1194/jlr.M000125. Epub 2009 Nov 2.
Phospholipid transfer protein (PLTP) belongs to the lipid transfer/lipopolysaccharide-binding protein gene family. Expression of PLTP has been implicated in the development of atherosclerosis. We evaluated the effects of PLTP region tagging single nucleotide polymorphisms (SNPs) on the prediction of both carotid artery disease (CAAD) and PLTP activity. CAAD effects were evaluated in 442 Caucasian male subjects with severe CAAD and 497 vascular disease-free controls. SNP prediction of PLTP transfer activity was evaluated in both a subsample of 87 subjects enriched for an allele of interest and in a confirmation sample of 210 Caucasian males and females. Hemoglobin A1c or insulin level predicted 11-14% of age- and sex-adjusted PLTP activity. PLTP SNPs that predicted approximately 11-30% of adjusted PLTP activity variance were identified in the two cohorts. For rs6065904, the allele that was associated with CAAD was also associated with elevated PLTP activity in both cohorts. SNPs associated with PLTP activity also predicted variation in LDL-cholesterol and LDL-B level only in the replication cohort. These results demonstrate that PLTP activity is strongly influenced by PLTP region polymorphisms and metabolic factors.
磷脂转移蛋白（PLTP）属于脂质转移/脂多糖结合蛋白基因家族。PLTP 的表达与动脉粥样硬化的发展有关。我们评估了 PLTP 区域标记单核苷酸多态性（SNP）对颈动脉疾病（CAAD）和 PLTP 活性预测的影响。在 442 名患有严重 CAAD 的高加索男性和 497 名无血管疾病对照者中评估 CAAD 效应。在一个包含感兴趣等位基因的 87 名受试者亚组和 210 名高加索男性和女性的确认样本中，评估了 SNP 对 PLTP 转移活性的预测。血红蛋白 A1c 或胰岛素水平预测了年龄和性别调整后 PLTP 活性的 11-14%。在两个队列中确定了预测约 11-30%调整后 PLTP 活性方差的 PLTP SNP。对于 rs6065904，与 CAAD 相关的等位基因也与两个队列中的 PLTP 活性升高相关。与 PLTP 活性相关的 SNP 也仅在复制队列中预测 LDL-胆固醇和 LDL-B 水平的变化。这些结果表明，PLTP 活性受 PLTP 区域多态性和代谢因素的强烈影响。
