Cheaib Miriam, Hornung Nicola, Dragano Nico, Frank Mirjam, Hoffmann Per, Nöthen Markus M, Erbel Raimund, Stang Andreas, Schmidt Börge
Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45122, Essen, Germany.
Institute of Medical Sociology, Centre for Health and Society, Medical Faculty and University Hospital, University of Düsseldorf, Düsseldorf, Germany.
Sci Rep. 2024 Dec 23;14(1):30612. doi: 10.1038/s41598-024-83437-w.
C-Reactive Protein (CRP) values are partly determined by variation at the CRP gene locus, but also influenced by socioeconomic position (SEP) and related lifestyle factors. As gene-by-SEP interactions have been suggested for traits associated with CRP and SEP (e.g., BMI, coronary artery disease), the aim of this study was to investigate the strength of a possible interaction between a CRP gene common variant (rs4287174) and SEP in their joint influence on CRP levels in a population-based study sample.
Single nucleotide polymorphism rs4287174 was genotyped in 4065 participants (aged 45-75 years) of the Heinz Nixdorf Recall study, a population-based prospective cohort. SEP indicators (education and income), risk factors (i.e., body mass index (BMI), total cholesterol, diabetes mellitus, coronary artery calcification, current smoking, hypertension, diet, no exercise) and blood serum CRP (mg/dl) were assessed at study baseline. Interaction analysis was based on linear regression and on stratified analyses (genetic effect stratified by SEP and vice versa) adjusted for age and sex using log(CRP + 1) as dependent variable.
Low SEP and rs4287174 T allele were both associated with higher CRP values. The strongest genetic effect was observed in the lowest educational group (≤ 10 years of education) with an exp(β) indicating 1.058-fold (95%-CI: 1.018; 1.100) average CRP values per additional T allele, while in the highest educational group (≥ 18 years) the association was considerably less strong (exp(β): 1.005 (95%-CI: 0.975; 1.037)). After including rs4287174-by-education interaction terms in the regression analysis, interaction was indicated suggesting stronger genetic effects on CRP in low SEP groups (exp(β): 1.056 (95%-CI: 1.005; 1.108); p = 0.029). The observed interaction did not seem to be substantially mediated by the risk factors included in the analysis. No indication for rs4287174-by-income interaction was observed.
Results imply that genetic effects of the CRP locus are modified by education as an indicator of life course SEP.
C反应蛋白（CRP）值部分由CRP基因位点的变异决定，但也受社会经济地位（SEP）及相关生活方式因素的影响。由于已有人提出与CRP和SEP相关的性状（如体重指数、冠状动脉疾病）存在基因与SEP的相互作用，本研究的目的是在一项基于人群的研究样本中，调查CRP基因常见变异（rs4287174）与SEP之间可能存在的相互作用对CRP水平的联合影响强度。
在海因茨·尼克斯多夫召回研究的4065名参与者（年龄45 - 75岁）中对单核苷酸多态性rs4287174进行基因分型，该研究是一项基于人群的前瞻性队列研究。在研究基线时评估SEP指标（教育程度和收入）、危险因素（即体重指数（BMI）、总胆固醇、糖尿病、冠状动脉钙化、当前吸烟状况、高血压、饮食、缺乏运动）以及血清CRP（mg/dl）。交互分析基于线性回归和分层分析（按SEP分层的遗传效应以及反之亦然），以log(CRP + 1)作为因变量，对年龄和性别进行了校正。
低SEP和rs4287174 T等位基因均与较高的CRP值相关。在教育程度最低组（≤10年教育）观察到最强的遗传效应，每增加一个T等位基因，exp(β)表明平均CRP值为1.058倍（95%置信区间：1.018；1.100），而在教育程度最高组（≥18年）这种关联则弱得多（exp(β)：1.005（95%置信区间：0.975；1.037））。在回归分析中纳入rs4287174与教育程度的交互项后，表明存在交互作用，提示在低SEP组中对CRP的遗传效应更强（exp(β)：1.056（95%置信区间：1.005；1.108）；p = 0.029）。观察到的交互作用似乎并未被分析中纳入的危险因素实质性介导。未观察到rs4287174与收入的交互作用迹象。
结果表明，CRP基因座的遗传效应会因作为生命历程SEP指标的教育程度而改变。
