Interaction between adolescent obesity and HLA risk genes in the etiology of multiple sclerosis.
Interaction between adolescent obesity and HLA risk genes in the etiology of multiple sclerosis.
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DOI：
10.1212/wnl.0000000000000203
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发表时间：
2014-03-11
期刊：
影响因子：
9.9
通讯作者：
Alfredsson L
中科院分区：
文献类型：
--
作者：
Hedström AK;Lima Bomfim I;Barcellos L;Gianfrancesco M;Schaefer C;Kockum I;Olsson T;Alfredsson L
我们研究了人类白细胞抗原（HLA）基因型和身体质量指数（BMI）状态与多发性硬化症（MS）发生风险之间的潜在相互作用。我们使用了2个病例对照研究，一个是事件病例（1510例，2017例对照），另一个是流行病例（937例，609例对照）。采用logistic回归计算95%可信区间（ci）的优势比（ORs），比较不同基因型和BMI受试者的MS发病率。通过计算相互作用的归因比例来评估基因型与BMI之间潜在的相互作用。在这两个队列中，无论HLA-A*02状态如何，HLA-DRB1*15与肥胖之间都存在显著的相互作用。同样，无论DRB1*15状态如何，缺乏a *02与肥胖之间存在显著的相互作用。在事件队列中，具有最易感基因型（携带DRB1*15和缺乏A*02）的肥胖受试者与没有遗传危险因素的非肥胖受试者相比，OR为16.2 （95% CI为7.5-35.2）。在流行研究中相应的OR为13.8 （95% CI 4.1-46.8）。我们观察到BMI状态和HLA基因型之间关于MS风险的显著相互作用。假设，肥胖固有的低度炎症反应与免疫系统的适应性、HLA分子限制臂协同作用，导致多发性硬化症，因此预防青少年肥胖可能降低发生多发性硬化症的风险，特别是在遗传易感性人群中。
We investigated potential interactions between human leukocyte antigen (HLA) genotype and body mass index (BMI) status in relation to the risk of developing multiple sclerosis (MS). We used 2 case-control studies, one with incident cases (1,510 cases, 2,017 controls) and one with prevalent cases (937 cases, 609 controls). Subjects with different genotypes and BMI were compared with regard to incidence of MS by calculating odds ratios (ORs) with 95% confidence intervals (CIs) employing logistic regression. Potential interactions between genotypes and BMI were evaluated by calculating the attributable proportion due to interaction. In both cohorts, a significant interaction was observed between HLA-DRB1*15 and obesity, regardless of HLA-A*02 status. Similarly, there was a significant interaction between absence of A*02 and obesity, regardless of DRB1*15 status. In the incident cohort, obese subjects with the most susceptible genotype (carriage of DRB1*15 and absence of A*02) had an OR of 16.2 (95% CI 7.5–35.2) compared to nonobese subjects without the genetic risk factors. The corresponding OR in the prevalent study was 13.8 (95% CI 4.1–46.8). We observed striking interactions between BMI status and HLA genotype with regard to MS risk. Hypothetically, a low-grade inflammatory response inherent to obesity synergizes with the adaptive, HLA molecule–restricted arm of the immune system, causing MS. Prevention of adolescent obesity may thus lower the risk of developing MS, predominantly among people with a genetic susceptibility to the disease.