PURPOSE

To investigate a causal relationship between Vitamin D levels and non-infectious uveitis and scleritis using Mendelian randomization (MR) techniques.

DESIGN

Two-sample Mendelian randomization case-control study.

METHODS

The study setting was a biobank of an academic, integrated health care system. The patient population comprised 375 case patients with a non-infectious uveitis and/or scleritis diagnosis and no diagnosis of infectious, trauma-related, or drug-induced uveitis/scleritis. In addition, there were 4167 controls with no uveitis or scleritis diagnosis. Causal effect estimates of low 25-hydroxy Vitamin D (25OHD) on uveitis/scleritis risk were calculated.

RESULTS

We found an association of genetically decreased 25OHD with uveitis/scleritis risk (odds ratio [OR] = 2.16, 95% CI = 1.01-4.64, P = .049, per SD decrease in log25OHD). In a first sensitivity MR analysis excluding the genetic variants that are unlikely to have a role in biologically active 25OHD, effect estimates were consistent with those from the primary analysis (OR = 2.38, 95% CI =1.06-5.36, P = 0.035, per SD of log25OHD). Furthermore, in a second sensitivity analysis using only the 6 variants within the CYP2R1 locus (which encodes 25OHD hydroxylase, the liver enzyme responsible for converting Vitamin D to 25OHD), genetically decreased 25OHD was strongly associated with increased uveitis/scleritis risk (OR = 6.42, 95% CI = 3.19-12.89, P = 1.7 × 10⁻⁷, per SD of log25OHD).

CONCLUSIONS

Our findings suggest a causal relationship between low Vitamin D levels and higher risk of non-infectious uveitis and scleritis. Vitamin D supplementation may be a low-cost, low-risk intervention to mitigate non-infectious uveitis and scleritis risk, and should be explored in a prospective trial.

中文翻译：

---

孟德尔随机化显示低维生素 D 对非感染性葡萄膜炎和巩膜炎风险的因果影响

目的

使用孟德尔随机化 (MR) 技术研究维生素 D 水平与非感染性葡萄膜炎和巩膜炎之间的因果关系。

设计

双样本孟德尔随机病例对照研究。

方法

研究环境是学术综合医疗保健系统的生物库。患者群体包括 375 例诊断为非感染性葡萄膜炎和/或巩膜炎且未诊断为感染性、创伤相关或药物引起的葡萄膜炎/巩膜炎的患者。此外，还有 4167 名对照者没有诊断出葡萄膜炎或巩膜炎。计算了低 25-羟基维生素 D (25OHD) 对葡萄膜炎/巩膜炎风险的因果效应估计。

结果

我们发现遗传性降低的 25OHD 与葡萄膜炎/巩膜炎风险相关（比值比 [OR] = 2.16，95% CI = 1.01-4.64，P  = .049，log25OHD 降低每 SD）。在排除不太可能在具有生物活性的 25OHD 中起作用的遗传变异的第一个敏感性 MR 分析中，效果估计与主要分析的结果一致（OR = 2.38，95% CI =1.06-5.36，P  = 0.035，每log25OHD 的标准差）。此外，在仅使用CYP2R1基因座（编码 25OHD 羟化酶，负责将维生素 D 转化为 25OHD 的肝酶）内的 6 个变体的第二个敏感性分析中，基因减少的 25OHD 与葡萄膜炎/巩膜炎风险增加密切相关（OR = 6.42 , 95% CI = 3.19-12.89, P = 1.7 × 10 ^-7，每个 log25OHD 的 SD）。

结论

我们的研究结果表明，低维生素 D 水平与非感染性葡萄膜炎和巩膜炎的高风险之间存在因果关系。补充维生素 D 可能是一种降低非感染性葡萄膜炎和巩膜炎风险的低成本、低风险干预措施，应在前瞻性试验中加以探索。