维生素 D 状态与动脉血压和高血压风险的关联：一项孟德尔随机研究。
Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study.
机构信息
Population, Policy and Practice, UCL Institute of Child Health, London, UK; Hugh Sinclair Unit of Human Nutrition, Department of Food & Nutritional Sciences, School of Chemistry, Food & Pharmacy, University of Reading, Reading, UK.
Population, Policy and Practice, UCL Institute of Child Health, London, UK.
出版信息
Lancet Diabetes Endocrinol. 2014 Sep;2(9):719-29. doi: 10.1016/S2213-8587(14)70113-5. Epub 2014 Jun 25.
BACKGROUND
Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk.
METHODS
In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium.
FINDINGS
In phenotypic analyses (up to n=49 363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, -0·12 mm Hg, 95% CI -0·20 to -0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97-0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, -0·02 mm Hg, -0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of -0·10 mm Hg in systolic blood pressure (-0·21 to -0·0001; p=0·0498) and a change of -0·08 mm Hg in diastolic blood pressure (-0·15 to -0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96-0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of -0·29 mm Hg in diastolic blood pressure (-0·52 to -0·07; p=0·01), a change of -0·37 mm Hg in systolic blood pressure (-0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87-0·97; p=0·002).
INTERPRETATION
Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.
FUNDING
British Heart Foundation, UK Medical Research Council, and Academy of Finland.
背景
低血浆 25-羟维生素 D（25[OH]D）浓度与高血压和高血压风险相关，但这种关联是否具有因果关系尚不清楚。我们使用孟德尔随机化方法来测试 25（OH）D 浓度是否与血压和高血压风险存在因果关系。
方法
在这项孟德尔随机化研究中，我们根据影响 25（OH）D 合成或底物可用性的基因（CYP2R1 和 DHCR7）的变异生成了一个等位基因评分（25[OH]D 合成评分），我们将其用作 25（OH）D 浓度的替代指标。我们对来自 35 项研究的多达 108173 名个体的数据进行了荟萃分析，以研究等位基因评分与血压测量之间的关联。我们用先前发表的来自国际血压联盟（ICBP）、心脏和衰老研究中的基因组流行病学（CHARGE）联盟和全球血压遗传学（Global BPGen）联盟的汇总统计数据补充了这些分析。
发现
在表型分析中（最多 n=49363），25（OH）D 浓度增加与收缩压降低相关（每增加 10%，-0.12mmHg，95%CI -0.20 至 -0.04；p=0.003），且降低高血压的几率（比值比[OR] 0.98，95%CI 0.97-0.99；p=0.0003），但与舒张压降低无关（每增加 10%，-0.02mmHg，-0.08 至 0.03；p=0.37）。在我们将 D-CarDia 和 ICBP 的数据进行合并分析的荟萃分析中（n=146581，排除重叠研究后），合成评分的每个 25（OH）D 增加等位基因与收缩压降低 0.10mmHg 相关（-0.21 至 -0.0001；p=0.0498）和舒张压降低 0.08mmHg 相关（-0.15 至 -0.02；p=0.01）。当 D-CarDia 和联盟的高血压数据一起进行荟萃分析时（n=142255），合成评分与降低高血压的几率相关（每个等位基因的 OR，0.98，0.96-0.99；p=0.001）。在工具变量分析中，每增加 10%的遗传上确定的 25（OH）D 浓度与舒张压降低 0.29mmHg 相关（-0.52 至 -0.07；p=0.01），收缩压降低 0.37mmHg 相关（-0.73 至 0.003；p=0.052），高血压的几率降低 8.1%（OR 0.92，0.87-0.97；p=0.002）。
解释
血浆 25（OH）D 浓度升高可能会降低高血压的风险。这一发现需要在一个独立的、同样有力的研究中进一步调查。
资金
英国心脏基金会、英国医学研究理事会和芬兰科学院。
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