背景:我们之前的研究发现,户外活动时间较少,作为阳光照射的代表,儿童多发性硬化症(POMS)的风险更高。紫外线辐射调节几个基因的表达,但目前尚不清楚这些基因是否能改变阳光照射对POMS风险的影响。
方法:在年龄和性别匹配的病例对照研究中,我们评估了在户外度过的时间与遗传非HLA风险变异之间的加性和乘法相互作用,以在紫外线辐射的代谢途径中发展POMS,包括CD28(RS6435203),CD86(rs9282641),和NFkB1(rs7665090)和前两个HLA危险因素(存在DRB1×15和不存在A*02)。
结果:在调整后的模型中(332个POMS案例,534个健康对照),与前夏季户外时间<30分钟/天相比,更多的时间和更高的紫外线辐射剂量与POMS的几率降低相关(OR分别为0.66,95%CI0.56-0.78,p<0.001;OR0.78,95%CI0.62-0.98,p=0.04).在危险因素之间没有发现明显的加性或乘性相互作用。
结论:探索发生MS的风险中的基因-环境相互作用可以揭示所涉及的潜在机制。虽然我们没有证据表明我们的候选基因有助于相互作用,其他基因可能。
BACKGROUND: Our previous study identified a significant association between lower time spent outdoors, as a proxy of sun exposure, and a higher risk of pediatric-onset multiple sclerosis (POMS). UV radiation modulates the expression of several genes, but it is unknown whether these genes modify the effect of sun exposure on POMS risk.
METHODS: In an age- and sex-matched case-control study, we evaluated the additive and multiplicative interactions between time spent outdoors and genetic non-HLA risk variants for developing POMS within the metabolic pathways of UV radiation, including CD28(rs6435203), CD86(rs9282641), and NFkB1(rs7665090) and the top two HLA risk factors (presence of DRB1×15 and absence of A*02).
RESULTS: In an adjusted model (332 POMS cases, 534 healthy controls), greater time compared to <30 min/day spent outdoors during the prior summer and higher UV radiation dose were associated with decreased odds of POMS (OR 0.66, 95% CI 0.56-0.78, p < 0.001; OR 0.78, 95 % CI 0.62-0.98, p = 0.04, respectively). No significant additive or multiplicative interactions were found between risk factors.
CONCLUSIONS: The exploration of gene-environment interactions in the risk of developing MS can unravel the underlying mechanisms involved. Although we do not have evidence that our candidate genes contribute to interactions, other genes may.