Department of Nutritional Sciences , University of Toronto , 150 College Street, Room 310 , Toronto , Ontario M5S 3E2 , Canada.
Li Ka Shing Knowledge Institute , St. Michael's Hospital , 209 Victoria Street , Toronto , Ontario M5B 1T8 , Canada.
J Proteome Res. 2018 Aug 3;17(8):2649-2656. doi: 10.1021/acs.jproteome.8b00117. Epub 2018 Jul 19.
Single nucleotide polymorphisms (SNPs) in the noncoding region of 9p21 have been associated with cardiovascular disease (CVD), but the mechanisms by which these genetic variants contribute to the pathogenesis of CVD remain unknown since no annotated proteins are present in this region of DNA. The objective of the current study was to determine if 9p21 genotypes are associated with distinct plasma proteins in young adults. Subjects were 1611 young adults aged 20-29 years from the Toronto Nutrigenomics and Health Study (1098 females and 513 males). DNA was isolated from fasting blood to analyze four SNPs in 9p21 (rs2383206, rs10757274, rs10757278, and rs1333049). Abundant plasma proteins ( n = 54) were measured using liquid chromatography multiple reaction monitoring mass spectrometry. Analysis of covariance was used to determine differences in plasma proteins between genotypes. In Caucasians ( n = 524), four SNPs were associated with apolipoprotein E and two with haptoglobin-β-chain concentration. In East Asians ( n = 388), three SNPs were associated with α-1b-Glycoprotein, two with apolipoprotein B-100, one with apolipoprotein E and one with haptoglobin-β-chain concentration. In South Asians ( n = 117), one SNP was associated with apolipoprotein B-100 concentration. Our findings suggest that 9p21 genotypes may play a role in various pathophysiological pathways that contribute to risk of CVD in early adulthood that might be distinct among different ethnocultural groups.
单核苷酸多态性（SNP）在非编码区域 9p21 已与心血管疾病（CVD）相关联，但这些遗传变异如何导致 CVD 的发病机制仍不清楚，因为在该 DNA 区域没有注释的蛋白质。本研究的目的是确定 9p21 基因型是否与年轻人的不同血浆蛋白相关。研究对象为来自多伦多营养基因组学和健康研究的 1611 名 20-29 岁的年轻人（1098 名女性和 513 名男性）。从空腹血液中分离 DNA 以分析 9p21 中的四个 SNP（rs2383206、rs10757274、rs10757278 和 rs1333049）。使用液相色谱多重反应监测质谱法测量丰富的血浆蛋白（n=54）。协方差分析用于确定基因型之间血浆蛋白的差异。在白种人（n=524）中，四个 SNP 与载脂蛋白 E 相关，两个与触珠蛋白-β 链浓度相关。在东亚人（n=388）中，三个 SNP 与α-1b-糖蛋白相关，两个与载脂蛋白 B-100 相关，一个与载脂蛋白 E 相关，一个与触珠蛋白-β 链浓度相关。在南亚人（n=117）中，一个 SNP 与载脂蛋白 B-100 浓度相关。我们的研究结果表明，9p21 基因型可能在导致年轻人 CVD 风险的各种病理生理途径中发挥作用，这些途径在不同的种族群体中可能是不同的。
