Harvard Medical School, Harvard University, 1309 Beacon Street, Brookline, MA, 02447, USA.
Department of Medicine, BIDMC Genomics, Proteomics, Bioinformatics, and Systems Biology Center, Beth Israel Deaconess Medical Center, Boston, USA.
Sci Rep. 2021 Jan 13;11(1):961. doi: 10.1038/s41598-020-79429-1.
Blood protein concentrations are clinically useful, predictive biomarkers of cardiovascular disease (CVD). Despite a higher burden of CVD among U.S. South Asians, no CVD-related proteomics study has been conducted in this sub-population. The aim of this study is to investigate the associations between plasma protein levels and CVD incidence, and to assess the potential influence of religiosity/spirituality (R/S) on significant protein-CVD associations, in South Asians from the MASALA Study. We used a nested case-control design of 50 participants with incident CVD and 50 sex- and age-matched controls. Plasma samples were analyzed by SOMAscan for expression of 1305 proteins. Multivariable logistic regression models and model selection using Akaike Information Criteria were performed on the proteins and clinical covariates, with further effect modification analyses conducted to assess the influence of R/S measures on significant associations between proteins and incident CVD events. We identified 36 proteins that were significantly expressed differentially among CVD cases compared to matched controls. These proteins are involved in immune cell recruitment, atherosclerosis, endothelial cell differentiation, and vascularization. A final multivariable model found three proteins (Contactin-5 [CNTN5], Low affinity immunoglobulin gamma Fc region receptor II-a [FCGR2A], and Complement factor B [CFB]) associated with incident CVD after adjustment for diabetes (AUC = 0.82). Religious struggles that exacerbate the adverse impact of stressful life events, significantly modified the effect of Contactin-5 and Complement factor B on risk of CVD. Our research is this first assessment of the relationship between protein concentrations and risk of CVD in a South Asian sample. Further research is needed to understand patterns of proteomic profiles across diverse ethnic communities, and the influence of resources for resiliency on proteomic signatures and ultimately, risk of CVD.
血液蛋白浓度是临床有用的心血管疾病（CVD）预测生物标志物。尽管美国南亚裔人群的 CVD 负担更高，但在该亚人群中尚未进行任何与 CVD 相关的蛋白质组学研究。本研究旨在探讨血浆蛋白水平与 CVD 发病的相关性，并评估宗教/精神信仰（R/S）对显著蛋白-CVD 相关性的潜在影响，研究对象来自 MASALA 研究中的南亚裔人群。我们使用了 50 例 CVD 发病患者和 50 例性别及年龄匹配对照者的巢式病例对照设计。采用 SOMAscan 技术检测 1305 种蛋白的表达水平。对蛋白和临床协变量进行多变量逻辑回归模型和 Akaike 信息准则模型选择分析，并进行进一步的效应修饰分析，以评估 R/S 措施对蛋白与 CVD 发病事件之间显著相关性的影响。我们确定了 36 种蛋白在 CVD 病例与匹配对照者之间存在显著差异表达。这些蛋白涉及免疫细胞募集、动脉粥样硬化、血管内皮细胞分化和血管生成。最终的多变量模型发现，在调整糖尿病后，有 3 种蛋白（Contactin-5 [CNTN5]、低亲和力免疫球蛋白γ Fc 区受体 II-a [FCGR2A]和补体因子 B [CFB]）与 CVD 发病相关（AUC=0.82）。宗教斗争加剧了生活应激事件的不利影响，显著改变了 Contactin-5 和补体因子 B 对 CVD 风险的影响。我们的研究首次评估了蛋白质浓度与南亚裔人群 CVD 风险之间的关系。需要进一步研究以了解不同族裔社区的蛋白质组特征模式，以及资源对蛋白质特征和最终 CVD 风险的弹性的影响。
