维生素D水平与易患哮喘、提高免疫球蛋白E水平和特应性皮炎的关系：一项孟德尔随机化研究
2017/07/24
摘要
背景：循环中低维生素D水平一直被认为与哮喘、特应性皮炎和免疫球蛋白E（IgE）水平升高的风险有关。由于缺乏维生素D十分常见且可纠正，因此，这些流行病学联系如真实存在则具有重要的公共卫生学意义。
方法和结果：本研究旨在验证遗传性低维生素D水平是否与哮喘、特应性皮炎和IgE水平升高的发生风险有关。通过运用孟德尔随机化（MR）方法控制由混杂因子和逆因果产生的偏倚。数据来源于英国生物样本库和SUNLIGHT、 GABRIEL 、EAGLE湿疹协会。采用33996名个体中的4个与25羟-维生素D（25OHD）水平密切相关的单核苷酸多态性（SNPs），进行MR研究以评估25OHD水平降低对哮喘（n = 146,761）、儿童期发病哮喘（n = 15,008）、特应性皮炎(n = 40,835)和IgE水平升高(n = 12,853)风险的影响，并用敏感性分析验证MR假说。
4个与25OHD降低相关的等位基因均与哮喘、特应性皮炎和提高的IgE水平无关(p ≥ 0.2)。25OHD水平的对数每降低一个标准差，对应的MR比值比（OR）在哮喘中为1.03（95%置信区间0.90-1.19, p =0.63），在儿童发作性哮喘中为0.95 (95% CI 0.69-1.31, p = 0.76)，在特应性皮炎中为1.12 (95% CI 0.92-1.37, p = 0.27)，在IgE水平的对数为-0.40 (95% CI -1.65 to 0.85, p = 0.54)。这些结果与评估人口分层、基因多效性和维生素D合成和代谢通路的敏感性分析保持一致。本研究的主要不足之处是调查未能排除结果与1,25二羟基维生素D（维生素D的活性形式）的联系，本研究在儿童型哮喘中无法检测到OR值小于1.33的效应，且分析局限于具有欧洲血统的白种人。本研究使用的数据来自英国生物样本库和SUNLIGHT, GABRIEL , EAGLE湿疹协会。
结论:本研究中未发现证据能证明遗传性的低维生素D水平会导致哮喘、特应性皮炎和免疫球蛋白E（IgE）水平升高的发生风险增加，表明增加维生素D水平可能不会降低特应性疾病发生的风险。
(复旦大学附属中山医院呼吸科 胡湘麟摘译 杨冬审校)
（PLoS Med. 2017 May 9;14(5):e1002294. doi: 10.1371/journal.pmed.1002294.eCollection 2017 May.）
Vitamin D levels and susceptibility to asthma, elevated immunoglobulin E levels,and atopic dermatitis: A Mendelian randomization study.
Manousaki D, Paternoster L, et al
Abstract
BACKGROUND:Low circulating vitamin D levels have been associated with risk of asthma, atopic dermatitis, and elevated total immunoglobulin E (IgE). These epidemiological associations, if true, would have public health importance, since vitamin D insufficiency is common and correctable.
METHODS AND FINDINGS:We aimed to test whether genetically lowered vitamin D levels were associated with risk of asthma, atopic dermatitis, or elevated serum IgE levels, using Mendelian randomization (MR) methodology to control bias owing to confounding and reverse causation. The study employed data from the UK Biobank resource and from the SUNLIGHT, GABRIEL and EAGLE eczema consortia. Using four single-nucleotide polymorphisms (SNPs) strongly associated with 25-hydroxyvitamin D (25OHD) levels in 33,996 individuals, we conducted MR studies to estimate the effect of lowered 25OHD on the risk of asthma (n = 146,761), childhood onset asthma (n = 15,008), atopic dermatitis (n = 40,835), and elevated IgE level (n = 12,853) and tested MR assumptions in sensitivity analyses. None of the four
25OHD-lowering alleles were associated with asthma, atopic dermatitis, or elevated IgE levels (p ≥ 0.2). The MR odds ratio per standard deviation decrease in log-transformed 25OHD was 1.03 (95% confidence interval [CI] 0.90-1.19, p =0.63) for asthma, 0.95 (95% CI 0.69-1.31, p = 0.76) for childhood-onset asthma, and 1.12 (95% CI 0.92-1.37, p = 0.27) for atopic dermatitis, and the effect size on log-transformed IgE levels was -0.40 (95% CI -1.65 to 0.85, p = 0.54). These results persisted in sensitivity analyses assessing population stratification and pleiotropy and vitamin D synthesis and metabolism pathways. The main limitations of this study are that the findings do not exclude an association between the studied outcomes and 1,25-dihydoxyvitamin D, the active form of vitamin D, the study was underpowered to detect effects smaller than an OR of 1.33 for childhood
asthma, and the analyses were restricted to white populations of European ancestry. This research has been conducted using the UK Biobank Resource and data from the SUNLIGHT, GABRIEL and EAGLE Eczema consortia.
CONCLUSIONS:In this study, we found no evidence that genetically determined reduction in 25OHD levels conferred an increased risk of asthma, atopic dermatitis, or elevated total serum IgE, suggesting that efforts to increase vitamin D are unlikely to reduce risks of atopic disease.
PLoS Med. 2017 May 9;14(5):e1002294. doi: 10.1371/journal.pmed.1002294.
eCollection 2017 May.
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