Wei Wenbin, Yang Song, Qiu Yingru, Wang Hairu, Zhao Xianghai, Zhao Yanping, Li Yun, Wu Ming, Chen Yanchun, Wang Wen, Shi Xiaoming, Liu Sijun, Chen Jinfeng, Shen Hongbing, Zhao David, Su Yanru, Shen Chong, Yao Ying-Shui
Department of Cardiology, The Fourth People's Hospital of Shenzhen City, Affiliated to Guangdong Medical College, Shenzhen City, 518033, China.
Mol Biol Rep. 2014;41(4):2335-43. doi: 10.1007/s11033-014-3087-8. Epub 2014 Jan 29.
C-reactive protein (CRP), an inflammatory marker that statistically predicts future cardiovascular risk, has been reported to be associated with plasma lipid level changes. Whether CRP genetic variants affect lipid metabolism is of importance to investigate. A community-based study population including 2,731 adult subjects aged 18-62 years was used to evaluate the association of CRP gene with dyslipidemia and five tagging SNPs (tagSNPs) were genotyped. Multiple logistic regression was applied to further evaluate relationships between the SNPs and lipid metabolism abnormality and general linear model was applied to compare plasma lipid levels between genotypes. Association analyses indicated that recessive model of SNPs rs876537 and rs4285692 had significant association with elevated HDL after adjustment for covariates. Odds ratio (OR) of rs876537 were 0.60 for HDL > 1.54 versus 1.04-1.54 mmol/L (P = 0.011), as well as, ORs were 0.617 for HDL > 1.83 versus ≤1.35 mmol/L (P = 0.002) and 0.724 for HDL = 1.59-1.83 versus ≤1.35 mmol/L (P = 0.028) respectively. OR of rs4285692 was 0.634 for HDL > 1.83 versus ≤1.35 mmol/L (P = 0.027). Further stratification analysis found significant associations of rs10737175 with elevated HDL (>1.54 vs. 1.04-1.54 mmol/L, OR 0.629 and P = 0.027) and elevated TG (≥1.70 vs. <1.70 mmol/L, ORs of additive and dominant models were 0.628, 0.545 and P values were 0.006, 0.003 respectively) in female. rs4285692 was significantly associated with elevated LDL (≥3.37 vs. <3.37 mmol/L), ORs equaled to 1.532, 2.281 for additive model and recessive model and P values were 0.028, 0.024 respectively in male. Furthermore, quantitative trait analysis indicated the variation T to C of rs876537 significantly affect decreased plasma HDL level (P = 0.014). Our findings suggest that CRP genetic polymorphisms independently had positive association with the risk of HDL, LDL and TG elevating and further replication in other large population and biological function research would be warranted.
C反应蛋白（CRP）是一种炎症标志物，经统计学分析可预测未来心血管疾病风险，据报道其与血浆脂质水平变化有关。CRP基因变异是否影响脂质代谢值得研究。本研究以一个基于社区的、包含2731名年龄在18至62岁之间的成年受试者的人群为对象，评估CRP基因与血脂异常的关联，并对5个标签单核苷酸多态性（tagSNP）进行基因分型。采用多因素logistic回归进一步评估单核苷酸多态性与脂质代谢异常之间的关系，并应用一般线性模型比较不同基因型之间的血浆脂质水平。关联分析表明，在校正协变量后，单核苷酸多态性rs876537和rs4285692的隐性模型与高密度脂蛋白（HDL）升高显著相关。对于HDL>1.54 mmol/L与1.04 - 1.54 mmol/L，rs876537的比值比（OR）为0.60（P = 0.011）；同样，对于HDL>1.83 mmol/L与≤1.35 mmol/L，OR为0.617（P = 0.002），对于HDL = 1.59 - 1.83 mmol/L与≤1.35 mmol/L，OR为0.724（P = 0.028）。对于HDL>1.83 mmol/L与≤1.35 mmol/L，rs4285692的OR为0.634（P = 0.027）。进一步的分层分析发现，rs10737175与女性HDL升高（>1.54 mmol/L与1.04 - 1.54 mmol/L，OR 0.629，P = 0.027）以及甘油三酯（TG）升高（≥1.70 mmol/L与<1.70 mmol/L，加性模型和显性模型的OR分别为0.628、0.545，P值分别为0.006、0.003）显著相关。在男性中，rs4285692与低密度脂蛋白（LDL）升高（≥3.37 mmol/L与<3.37 mmol/L）显著相关，加性模型和隐性模型的OR分别为1.532、2.281，P值分别为0.028、0.024。此外，数量性状分析表明，rs876537的T到C变异显著影响血浆HDL水平降低（P = 0.014）。我们的研究结果表明，CRP基因多态性独立地与HDL、LDL和TG升高的风险呈正相关，有必要在其他大样本人群中进一步验证并开展生物学功能研究。
