Paszkowiak Maria, Dorand Madisen Fae, Richards Jesse
University of Oklahoma, School of Community Medicine, 4502 E. 41st Street, Tulsa, OK, 74135, USA.
Department of Internal Medicine, University of Oklahoma, School of Community Medicine, 4502 E. 41st Street, Tulsa, OK, 74135, USA.
Obes Pillars. 2023 Feb 21;5:100059. doi: 10.1016/j.obpill.2023.100059. eCollection 2023 Mar.
Once thought to be primarily a result of lifestyle, it is now known that obesity has significant genetic components. Dozens of genes have been linked to obesity, and office-based genetic testing for obesity-associated genes is now readily available. As both pharmacotherapy and genetic testing for obesity become more accessible, pharmacogenetic personalization is becoming a reality. In this case report, a patient with a PLXNA4 polymorphism had a superior weight loss response to phentermine/topiramate therapy than has previously been reported in the literature. Thus, variants in PLXNA4 may provide a genetic basis for this patient's superior response to weight loss pharmacotherapy and cardiovascular risk factor reduction.
In this case study, office-based genetic testing was utilized to identify the presence of variants in nearly 80 genes that have been linked to obesity in a patient who had hyper-responsive weight loss results on phentermine/topiramate pharmacotherapy.
A variant of the PLXNA4 gene, which has known pathogenic variants linked to genetic obesity syndromes, was identified in this patient who had a superior weight loss response to phentermine/topiramate pharmacotherapy.
Due to overlapping molecular pathways, it is possible that PLXNA4 variants convey a superior weight-loss response and therefore superior cardiovascular risk factor reduction phentermine/topiramate therapy. Further studies are needed to examine the relationship between PLXNA4 variants and weight loss with phentermine/topiramate pharmacotherapy.
肥胖曾经被认为主要是生活方式导致的，现在已知其具有显著的遗传成分。数十种基因已被证实与肥胖有关，基于办公室的肥胖相关基因检测现已广泛可用。随着肥胖药物治疗和基因检测越来越容易获得，药物基因组个性化正成为现实。在本病例报告中，一名携带PLXNA4基因多态性的患者对苯丁胺/托吡酯治疗的减肥反应优于此前文献报道。因此，PLXNA4基因变异可能为该患者对减肥药物治疗及心血管危险因素降低的卓越反应提供遗传基础。
在本病例研究中，对一名在苯丁胺/托吡酯药物治疗中减肥反应超敏的患者，采用基于办公室的基因检测来识别近80种与肥胖相关基因的变异情况。
在该对苯丁胺/托吡酯药物治疗有卓越减肥反应的患者中，发现了PLXNA4基因的一种变异，已知该基因的致病性变异与遗传性肥胖综合征有关。
由于分子途径重叠，PLXNA4基因变异可能带来卓越的减肥反应，进而在苯丁胺/托吡酯治疗中更好地降低心血管危险因素。需要进一步研究来探讨PLXNA4基因变异与苯丁胺/托吡酯药物治疗减肥效果之间的关系。
