Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan.
School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan.
PLoS One. 2020 Mar 26;15(3):e0230715. doi: 10.1371/journal.pone.0230715. eCollection 2020.
Evidence suggests the existence of association between a large panel of modifiable biomarkers representing inflammation, coagulation, paraoxonase, and endothelial activation pathways and carotid atherosclerosis. Thus, this study investigated whether CRP, FGA, FGB, FGG, PON1, and EDNRA gene variants affected plasma hs-CRP, fibrinogen levels, and thickness of carotid intima media thickness (IMT). Nineteen single-nucleotide polymorphisms of CRP, FGA, FGB, FGG, PON1, and EDNRA genes were examined in 480 participants from 160 families. Carotid IMT was measured by ultrasound. Generalized linear models with generalized estimating equation were utilized to consider the dependence of subjects within families. In the recessive model, homozygotes for the minor alleles of rs1800789, rs1800790 and rs4220 SNPs in FGB gene indicated a reduced risk of IMT (Exp. β = 0.89, 0.89, 0.88), which remained significant after adjustment for confounding factors. Significant interaction effects between CRP SNP rs1130864 and rs3093059 and gender for IMT were observed with a significant association in men only. Men carrying minor-minor genotype of CRP SNP rs1130864 and rs3093059 had 0.70- and 0.78-fold lower IMT than men carrying minor-major/major-major genotype. We also observed that the interaction of CRP SNP rs1130864 and rs3093059 with obesity on IMT, hs-CRP and fibrinogen levels. These results support the hypothesis that inflammatory genes are involved in atherosclerosis, most likely via complex gene-gender and gene-obesity interactions.
有证据表明，大量代表炎症、凝血、对氧磷酶和内皮激活途径的可调节生物标志物与颈动脉粥样硬化之间存在关联。因此，本研究调查了 CRP、FGA、FGB、FGG、PON1 和 EDNRA 基因变异是否影响血浆 hs-CRP、纤维蛋白原水平和颈动脉内膜中层厚度（IMT）。在 160 个家庭的 480 名参与者中，检查了 CRP、FGA、FGB、FGG、PON1 和 EDNRA 基因的 19 个单核苷酸多态性。通过超声测量颈动脉 IMT。利用广义估计方程的广义线性模型考虑了个体在家庭内的依赖性。在隐性模型中，FGB 基因 rs1800789、rs1800790 和 rs4220 SNP 的次要等位基因纯合子表明 IMT 风险降低（Exp.β=0.89、0.89、0.88），调整混杂因素后仍有显著意义。CRP SNP rs1130864 和 rs3093059 与性别之间存在显著的 IMT 相互作用效应，仅在男性中存在显著相关性。携带 CRP SNP rs1130864 和 rs3093059 次要-次要基因型的男性 IMT 比携带次要-主要/主要-主要基因型的男性低 0.70-0.78 倍。我们还观察到 CRP SNP rs1130864 和 rs3093059 与肥胖对 IMT、hs-CRP 和纤维蛋白原水平的相互作用。这些结果支持炎症基因参与动脉粥样硬化的假说，这很可能是通过复杂的基因-性别和基因-肥胖相互作用。
