Association of high sensitive C-reactive protein with coronary heart disease: a Mendelian randomization study

• Published in: BMC medical genetics Vol. 20; no. 1; pp. 170 - 7
• Main Authors: Zhuang, Qian, Shen, Chong, Chen, Yanchun, Zhao, Xianghai, Wei, Pengfei, Sun, Junxiang, Ji, Yanni, Chen, Xiaotian, Yang, Song
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 06.11.2019; BioMed Central; BMC
• Subjects: Aged; Analysis; C-reactive protein; C-Reactive Protein - metabolism; Cardiovascular diseases; CHD; China; Coronary Disease - blood; Coronary Disease - genetics; Coronary heart disease; CRP gene; EDTA; Epidemiology; Female; Genes; Genetic aspects; Genetic research; Genetics; Genotypes; Heart diseases; Hs-CRP; Humans; Male; Medical research; Mendelian Randomization Analysis; Middle Aged; Polymorphism, Single Nucleotide; Regression analysis; Telecommunications equipment; Type 2 diabetes; China; CRP gene; Mendelian randomization analysis; Hs-CRP; CHD
• ISSN: 1471-2350; 1471-2350
• DOI: 10.1186/s12881-019-0910-z

Whether high sensitivity C-reactive protein (hs-CRP) has a causal effect on coronary heart disease (CHD) is unclear. This study investigated the causal effect of hs-CRP on CHD risk using Mendelian Randomization (MR) analysis. A total of 3802 subjects were recruited in the follow-up study. Linear regression model was used to evaluate the relationship between CRP polymorphisms and hs-CRP. Survival receiver operator characteristic curve method was used to explore the cut-off of hs-CRP on CHD incidence. Cox regression model was applied to detect the association of hs-CRP with CHD by calculating the hazard ratio (HR) and 95% confidence interval (CI). Rs1205 and rs876537 in CRP were selected as instrumental variables in MR analysis. During a median follow-up time of 5.01 years, 98 CHD incidence was identified (47.03/10 person-years). Hs-CRP was significantly increased among rs1205 and rs876537 genotypes with r values of 0.064 and 0.066, respectively. Hs-CRP 1.08 mg/L was identified as the cut-off value with a maximum value of sensitivity and specificity on prediction of CHD. Participants with ≥1.08 mg/L of hs-CRP has a higher risk of CHD incidence than that of participants with < 1.08 mg/L, the adjusted HR (95% CI) was 1.69 (1.11-2.60) with a P value of 0.016. No significant casual association was observed between hs-CRP and CHD with a P value of 0.777. The association between hs-CRP and CHD is unlikely to be causal, hs-CRP might be a predictor for incidence of CHD in general population.