目的:确定炎症生物标志物是否是更多近视性屈光不正的危险因素。
方法:瑞典北部人口健康研究(NSPHS),提供炎症生物标志物数据;英国生物银行,提供屈光不正数据。95,619名年龄在40至69岁之间的欧洲男性和女性,有屈光不正和炎症生物标记的可用信息。炎症生物标志物包括ADA,CCL23,CCL25,CD6,CD40,CDCP-1,CST5,CXCL-5,CXCL-6,CXCL-10,IL-10RB,IL-12B,IL-15RA,IL-18R1,MCP-2,MMP-1,TGF-β1,TNF-β,TWEAK和VEGF-A是暴露,使用公式SE=球体+(圆柱体/2)的球形当量(SE)是结果。
结果:孟德尔随机化分析显示,VEGF-A每增加一个单位,CD6,MCP-2与0.040D/pg的近视屈光度有因果关系。mL-1(95%置信区间0.019~0.062;P=2.031×10-4),0.042d/pg。mL-1(0.027~0.057;P=7.361×10-8)和0.016D/pg。mL-1(0.004至0.028;P=0.009),TWEAK的每单位增加与近视屈光不正0.104D/pg有因果关系。mL-1(-0.152至-0.055;P=2.878×10-5)。由MR-Egger测试,加权中位数,MR-PRESSO,省略一次的方法,我们的结果对VEGF-A的水平多效性和异质性是稳健的,MCP-2,CD6,但不在TWEAK。
结论:我们的孟德尔随机分析支持VEGF-A的因果效应,MCP-2、CD6和TWEAK对近视性屈光不正的影响。这些发现对于为近视的早期干预提供新的指标,使近视视力威胁的后果变得不那么不可避免是重要的。
OBJECTIVE: To determine whether inflammatory biomarkers are causal risk factors for more myopic refractive errors.
METHODS: Northern Sweden Population Health Study (NSPHS), providing inflammatory biomarkers data; UK Biobank, providing refractive errors data. 95,619 European men and women aged 40 to 69 years with available information of refractive errors and inflammatory biomakers. Inflammatory biomarkers including ADA, CCL23, CCL25, CD6, CD40, CDCP-1, CST5, CXCL-5, CXCL-6, CXCL-10, IL-10RB, IL-12B, IL-15RA, IL-18R1, MCP-2, MMP-1, TGF-β1, TNF-β, TWEAK and VEGF-A were exposures, and spherical equivalent (SE) using the formula SE = sphere + (cylinder/2) was outcome.
RESULTS: Mendelian randomization analyses showed that each unit increase in VEGF-A, CD6, MCP-2 were causally related to a more myopic refractive errors of 0.040 D/pg.mL-1 (95% confidence interval 0.019 to 0.062; P = 2.031 × 10-4), 0.042 D/pg.mL-1 (0.027 to 0.057; P = 7.361 × 10-8) and 0.016 D/pg.mL-1 (0.004 to 0.028; P = 0.009), and each unit increase in TWEAK was causally related to a less myopic refractive errors of 0.104 D/pg.mL-1 (-0.152 to -0.055; P = 2.878 × 10-5). Tested by the MR-Egger, weighted median, MR-PRESSO, Leave-one-out methods, our results were robust to horizontal pleiotropy and heterogeneity in VEGF-A, MCP-2, CD6, but not in TWEAK.
CONCLUSIONS: Our Mendelian Randomization analysis supported the causal effects of VEGF-A, MCP-2, CD6 and TWEAK on myopic refractive errors. These findings are important for providing new indicators for early intervention of myopia to make myopic eyesight threatening consequences less inevitable.