Patients with anorexia nervosa have an increased burden of rare, damaging mutations in the BBOX1 gene.

IF 4.5 3区 医学 Q2 NUTRITION & DIETETICS
Michael Lutter
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Abstract

Background: People with anorexia nervosa (AN) exhibit a strong aversion to eating calorically dense foods, especially those high in fat. It has previously been reported that these patients display altered metabolism of fatty acids, however it is unclear if these metabolic disturbances represent a primary biological substrate underlying predisposition to restrictive eating behaviors or occur secondarily to malnutrition.

Methods: We report the frequency of rare (minor allele frequency < 1%), damaging (CADD > 15) mutations in the BBOX1 gene of 183 patients with anorexia nervosa who received whole exome sequencing (WES) as part of their psychiatric evaluation. The observed frequency from our cohort was then compared to the rate of rare, damaging mutations in BBOX1 reported in the gnomAD database to determine if there was an excessive burden of damaging mutations.

Results: The 11-27127338-G-A single nucleotide polymorphism in BBOX1 was observed to be shared by four sisters with a history of AN. Subsequent analysis found that this variant was also present in five out of 182 patients who had WES results. Six more unrelated patients out of 182 were found to have one of five additional rare, damaging mutations in BBOX1. In total, 12 out of 183 patients (6.6%) with AN were found to have a rare, damaging mutation in BBOX1 compared to an expected count of 4.4 (2.4%) from the gnomAD database (odds ratio 2.86; p = 0.0117).

Conclusions: Patients with a history of AN have an increased burden of rare, damaging mutations in the BBOX1 gene. Because BBOX1 is required for synthesis of carnitine, a nutrient required for transport of long-chain fatty acids into the mitochondria for beta-oxidation, this finding suggests that impaired utilization of long-chain fatty acids may increase the risk of developing AN in a subset of patients. Identification of this group of patients by genetic or blood testing may lead to improved treatment outcomes and/or secondary prevention of relapse.

Abstract Image

神经性厌食症患者BBOX1基因中罕见的、破坏性的突变负担增加。
背景:神经性厌食症(AN)患者对高热量食物,尤其是高脂肪食物表现出强烈的厌恶。此前有报道称,这些患者表现出脂肪酸代谢改变,但尚不清楚这些代谢紊乱是限制性饮食行为易感的主要生物学基础,还是营养不良的继发。方法:我们报告了183例神经性厌食症患者BBOX1基因罕见(小等位基因频率15)突变的频率,这些患者接受了全外显子组测序(WES)作为其精神病学评估的一部分。然后将从我们的队列中观察到的频率与gnomAD数据库中报道的BBOX1罕见的破坏性突变率进行比较,以确定是否存在过度的破坏性突变负担。结果:4例有AN病史的姐妹存在BBOX1基因11-27127338-G-A单核苷酸多态性。随后的分析发现,182名有WES结果的患者中有5人也存在这种变异。在182名患者中,又有6名不相关的患者被发现有另外5种罕见的、破坏性的BBOX1突变中的一种。总的来说,183名AN患者中有12名(6.6%)被发现有罕见的、破坏性的BBOX1突变,而gnomAD数据库的预期计数为4.4名(2.4%)(优势比2.86;p = 0.0117)。结论:有AN病史的患者BBOX1基因的罕见、破坏性突变负担增加。由于BBOX1是合成肉碱所必需的,肉碱是将长链脂肪酸运输到线粒体进行β氧化所需的营养物质,这一发现表明,对长链脂肪酸的利用受损可能会增加一部分患者发生AN的风险。通过基因或血液检测识别这组患者可能会改善治疗结果和/或二次预防复发。
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来源期刊
Journal of Eating Disorders
Journal of Eating Disorders Neuroscience-Behavioral Neuroscience
CiteScore
5.30
自引率
17.10%
发文量
161
审稿时长
16 weeks
期刊介绍: Journal of Eating Disorders is the first open access, peer-reviewed journal publishing leading research in the science and clinical practice of eating disorders. It disseminates research that provides answers to the important issues and key challenges in the field of eating disorders and to facilitate translation of evidence into practice. The journal publishes research on all aspects of eating disorders namely their epidemiology, nature, determinants, neurobiology, prevention, treatment and outcomes. The scope includes, but is not limited to anorexia nervosa, bulimia nervosa, binge eating disorder and other eating disorders. Related areas such as important co-morbidities, obesity, body image, appetite, food and eating are also included. Articles about research methodology and assessment are welcomed where they advance the field of eating disorders.
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