降脂药与儿童自身免疫性疾病因果关系的药物靶向孟德尔随机化研究  

Drug-targeted Mendelian Randomization Study on the Causal Relationship Between Lipid-lowering Drugs and Autoimmune Diseases in Children

作　　者：孔德进 孔祥斌 张景秀 高阳 KONG Dejin;KONG Xiangbin;ZHANG Jingxiu;GAO Yang(Department of Pediatric,Linyi Central Hospital,Linyi 276400,Shandong,China;Department of Otolaryngology,Linyi Central Hospital,Linyi 276400,Shandong,China)

机构地区：[1]临沂市中心医院儿科,山东临沂276400 [2]临沂市中心医院耳鼻喉科,山东临沂276400

出　　处：《医学信息》2025年第3期91-96,共6页Journal of Medical Information

摘　　要：目的分析影响降脂药物靶点表达或功能的遗传变异是否与儿童自身免疫性疾病风险相关。方法使用HMGCR(编码他汀类药物的靶点)、PCSK9(编码PCSK9抑制剂的靶点)和APOB(编码米泊美生的靶点)降脂药物的蛋白靶点编码基因的变异体进行孟德尔随机化分析。使用药物靶点孟德尔随机化(MR)分析靶向抑制剂对不同自身免疫性疾病的影响。结果抑制HMGCR靶点的表达对儿童1型糖尿病保护作用[IVW法:OR(95%CI)=0.5996(0.3714~0.8277),P=1.11×10^(-5);加权中位数法:OR(95%CI)=0.6555(0.3725~0.9385),P=0.0034]。抑制APOB靶点对幼年特发性关节炎[IVW法:OR(95%CI)=0.3053(-0.3960~1.0066),P=9.130×10^(-4);加权中位数法:OR(95%CI)=0.3599(-0.5955~1.3152),P=0.0036]和早发型重症肌无力[IVW法:OR(95%CI)=0.2361(-0.4439~0.9162),P=3.182×10^(-5);加权中位数法:OR(95%CI)=0.3192(-0.5376~1.1760),P=0.0090]有保护作用。APOB抑制剂对儿童甲状腺炎在IVW法有保护作用[OR(95%CI)=0.3849(-0.5495~1.3193),P=0.0452],加权中位法无统计学意义[OR(95%CI)=0.3821(-0.6843~1.4485),P=0.0770]。抑制PCSK9、HMGCR和APOB靶点与川崎病、乳糜泻和银屑病的风险均无显著相关性。结论降脂药可能通过靶点对儿童1型糖尿病、幼年特发性关节炎、早发型重症肌无力及儿童甲状腺炎有保护作用,但临床应用仍需谨慎。Objective To analyze whether genetic variations affecting the expression or function of lipid-lowering drug targets are associated with the risk of autoimmune diseases in children.Methods Mendelian randomization analysis was performed using HMGCR(encoding the target of statins),PCSK9(encoding the target of PCSK9 inhibitors),and APOB(encoding the target of milpometasone).Mendelian randomization(MR)was used to analyze the effects of targeted inhibitors on different autoimmune diseases.Results Inhibition of HMGCR target expression had a protective effect on type 1 diabetes mellitus in children[IVW method:OR(95%CI)=0.5996(0.3714-0.8277),P=1.11×10^(-5);weighted median method:OR(95%CI)=0.6555(0.3725-0.9385),P=0.0034].Inhibition of APOB targets had a protective effect on adolescent idiopathic arthritis[IVW method:OR(95%CI)=0.3053(-0.3960-1.0066),P=9.130×10^(-4);weighted median method:OR(95%CI)=0.3599(-0.5955-1.3152),P=0.0036]and early-onset myasthenia gravis[IVW method:OR(95%CI)=0.2361(-0.4439-0.9162),P=3.182×10^(-5);weighted median method:OR(95%CI)=0.3192(-0.5376-1.1760),P=0.0090].APOB inhibitor had a protective effect on children's thyroiditis in IVW method[OR(95%CI)=0.3849(-0.5495-1.3193),P=0.0452],and there was no statistical significance in weighted median method[OR(95%CI)=0.3821(-0.6843-1.4485),P=0.0770].Inhibition of PCSK9,HMGCR,and APOB targets was not significantly associated with the risk of Kawasaki disease,celiac disease,and psoriasis.Conclusion Lipid-lowering drugs may have protective effects on children with type 1 diabetes mellitus,adolescent idiopathic arthritis,early-onset myasthenia gravis and thyroiditis in children through targets,but clinical application still needs to be cautious.

关 键 词：降血脂药 自身免疫疾病 3-羟基-3-甲基戊二酰辅酶A还原酶 前蛋白转化酶枯草溶菌素9 载脂蛋白B类 

分 类 号：R593.2[医药卫生—内科学]