Vanda Pharmaceuticals Inc., Pennsylvania NW, Washington, District of Columbia, USA.
Clin Transl Gastroenterol. 2022 Apr 1;13(4):e00474. doi: 10.14309/ctg.0000000000000474.
Gastroparesis is a serious medical condition characterized by delayed gastric emptying and symptoms of nausea, vomiting, bloating, fullness after meals, and abdominal pain.
To ascertain the genetic risk factors for gastroparesis, we conducted the largest thus far whole-genome sequencing study of gastroparesis. We investigated the frequency and effect of rare loss-of-function variants in patients with both idiopathic and diabetic gastroparesis enrolled in a clinical study of gastroparesis.
Among rare loss-of-function variants, we reported an increased frequency of a frameshift mutation p.Leu202ArgfsTer105, within the motilin receptor gene, variant rs562138828 (odds ratio 4.9). We currently replicated this finding in an independent large cohort of gastroparesis samples obtained from patients participating in the ongoing phase III gastroparesis clinical study.
Motilin receptor is an important therapeutic target for the treatment of hypomotility disorders. The identified genetic variants may be important risk factors for disease as well as may inform treatments, especially those targeting motilin receptor.
胃轻瘫是一种严重的医学病症，其特征为胃排空延迟，以及恶心、呕吐、腹胀、饱胀感、餐后腹痛等症状。
为了确定胃轻瘫的遗传风险因素，我们进行了迄今为止最大规模的胃轻瘫全基因组测序研究。我们研究了在一项胃轻瘫临床研究中招募的特发性和糖尿病性胃轻瘫患者中罕见的功能丧失性变体的频率和影响。
在罕见的功能丧失性变体中，我们报告了在胃动素受体基因内的移码突变 p.Leu202ArgfsTer105 内的频率增加，变体 rs562138828（比值比 4.9）。我们目前在一项正在进行的胃轻瘫临床研究中从参与的患者中获得的胃轻瘫样本的独立大队列中复制了这一发现。
胃动素受体是治疗低动力障碍的重要治疗靶点。所鉴定的遗传变体可能是疾病的重要风险因素，并且可能为治疗方法提供信息，特别是那些针对胃动素受体的治疗方法。
