Department of Internal and Agricultural Medicine, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland (M.S., E.J., T.J.G.).
Institute of Cardiovascular and Medical Sciences (M.S., P.W., N.S., T.J.G.), University of Glasgow, United Kingdom.
Circulation. 2020 Apr 21;141(16):1307-1317. doi: 10.1161/CIRCULATIONAHA.119.045102. Epub 2020 Mar 9.
High blood pressure (BP) is a risk factor for cardiovascular morbidity and mortality. While BP is regulated by the function of kidney, vasculature, and sympathetic nervous system, recent experimental data suggest that immune cells may play a role in hypertension.
We studied the relationship between major white blood cell types and blood pressure in the UK Biobank population and used Mendelian randomization (MR) analyses using the ≈750 000 UK-Biobank/International Consortium of Blood Pressure-Genome-Wide Association Studies to examine which leukocyte populations may be causally linked to BP.
A positive association between quintiles of lymphocyte, monocyte, and neutrophil counts, and increased systolic BP, diastolic BP, and pulse pressure was observed (eg, adjusted systolic BP mean±SE for 1st versus 5th quintile respectively: 140.13±0.08 versus 141.62±0.07 mm Hg for lymphocyte, 139.51±0.08 versus 141.84±0.07 mm Hg for monocyte, and 137.96±0.08 versus 142.71±0.07 mm Hg for neutrophil counts; all <10). Using 121 single nucleotide polymorphisms in MR, implemented through the inverse-variance weighted approach, we identified a potential causal relationship of lymphocyte count with systolic BP and diastolic BP (causal estimates: 0.69 [95% CI, 0.19-1.20] and 0.56 [95% CI, 0.23-0.90] of mm Hg per 1 SD genetically elevated lymphocyte count, respectively), which was directionally concordant to the observational findings. These inverse-variance weighted estimates were consistent with other robust MR methods. The exclusion of rs3184504 SNP in the locus attenuated the magnitude of the signal in some of the MR analyses. MR in the reverse direction found evidence of positive effects of BP indices on counts of monocytes, neutrophils, and eosinophils but not lymphocytes or basophils. Subsequent MR testing of lymphocyte count in the context of genetic correlation with renal function or resting and postexercise heart rate demonstrated a positive association of lymphocyte count with urine albumin-to-creatinine ratio.
Observational and genetic analyses demonstrate a concordant, positive and potentially causal relationship of lymphocyte count with systolic BP and diastolic BP.
高血压（BP）是心血管发病率和死亡率的一个风险因素。虽然 BP 的调节受到肾脏、血管和交感神经系统的功能影响，但最近的实验数据表明，免疫细胞可能在高血压中发挥作用。
我们在英国生物库人群中研究了主要白细胞类型与血压之间的关系，并使用孟德尔随机分析（MR），使用 ≈75 万英国生物库/国际血压基因组-全基因组关联研究联盟来检查哪些白细胞群体可能与 BP 有因果关系。
观察到淋巴细胞、单核细胞和中性粒细胞计数的五分位数与收缩压、舒张压和脉压呈正相关（例如，第 1 与第 5 五分位的调整后收缩压平均值±SE：淋巴细胞分别为 140.13±0.08 与 141.62±0.07mmHg，单核细胞分别为 139.51±0.08 与 141.84±0.07mmHg，中性粒细胞分别为 137.96±0.08 与 142.71±0.07mmHg；所有<10）。通过逆方差加权方法，使用 121 个单核苷酸多态性进行的 MR 分析，我们确定了淋巴细胞计数与收缩压和舒张压之间潜在的因果关系（因果估计值：0.69[95%CI，0.19-1.20]和 0.56[95%CI，0.23-0.90]每 1 个标准差升高的淋巴细胞计数的 mm Hg），这与观察结果一致。这些逆方差加权估计与其他稳健的 MR 方法一致。在 rs3184504 SNP 排除在 基因座后，一些 MR 分析中的信号幅度减弱。相反方向的 MR 分析发现，BP 指数对单核细胞、中性粒细胞和嗜酸性粒细胞计数有正向影响，但对淋巴细胞或嗜碱性粒细胞没有影响。随后在肾功能或静息和运动后心率的遗传相关性背景下对淋巴细胞计数进行 MR 测试，表明淋巴细胞计数与尿白蛋白/肌酐比值呈正相关。
观察性和遗传分析表明，淋巴细胞计数与收缩压和舒张压之间存在一致、正向和潜在的因果关系。
