A genetic variant in proximity to the gene <i>LYPLAL1</i> is associated with lower hunger feelings and increased weight loss following Roux-en-Y gastric bypass surgery

<b>Objective:</b> Bariatric surgery is the most efficient treatment of severe obesity. We investigated to what extent BMI- or waist-hip ratio (WHR)-related genetic variants are associated with excess BMI loss (EBMIL) two years after Roux-en-Y gastric bypass (RYGB) surgery, and elucidated the affected biological pathways. <b>Methods:</b> Two-hundred fifty-one obese patients (age: 43 ± 10.7, preoperative BMI: 45.1 ± 6.1 kg/m², 186 women) underwent RYGB surgery and were followed up after two years with regard to BMI. Patients were genotyped for 32 single-nucleotide polymorphisms (SNPs) that were investigated with regard to their impact on response to RYGB and preoperatively measured Three Factor Eating Questionnaire (TFEQ) scores. <b>Results:</b> Homozygous T carriers of the SNP rs4846567 in proximity to the Lysophospholipase-like 1 (<i>LYPLAL1</i>) gene showed a 7% higher EBMIL compared to wild-type and heterozygous carriers (<i>p</i> = 0.031). TT-allele carriers showed furthermore lower scores for Hunger (74%, <i>p</i> p p = 0.017) than GG/GT carriers in the TFEQ. Patients within the lowest quartile of Hunger scores had a 32% greater EBMIL compared to patients in the highest quartile (<i>p</i> <b>Conclusion:</b> The <i>LYPLAL1</i> genotype is associated with differences in eating behavior and loss of extensive body weight following RYGB surgery. Genotyping and the use of eating behavior-related questionnaires may help to estimate the RYGB-associated therapy success.<b>研究目标：</b> 减重代谢手术（Bariatric surgery）是治疗重度肥胖的最有效手段。本研究拟探讨与体重指数（Body Mass Index, BMI）或腰臀比（waist-hip ratio, WHR）相关的遗传变异，与Roux-en-Y胃旁路术（Roux-en-Y gastric bypass, RYGB）术后2年的体质量指数超额丢失量（excess BMI loss, EBMIL）之间的关联，并阐明其所涉及的生物学通路。<b>研究方法：</b> 本研究共纳入251例肥胖患者（年龄：43±10.7岁，术前BMI：45.1±6.1 kg/m²，女性186例），均接受RYGB手术，并于术后2年对其BMI进行随访监测。所有患者针对32个单核苷酸多态性位点（single-nucleotide polymorphisms, SNPs）进行基因分型，分析上述位点对RYGB手术应答的影响，并检测患者术前的三因素饮食问卷（Three Factor Eating Questionnaire, TFEQ）评分。<b>研究结果：</b> 位于溶血磷脂酶样1基因（<i>LYPLAL1</i>）邻近区域的SNP rs4846567的纯合T等位基因携带者，其EBMIL较野生型及杂合子携带者高出7%（<i>p</i> = 0.031）。在TFEQ评分中，TT等位基因携带者的饥饿感评分（74%，<i>p</i> = 0.017）显著低于GG/GT基因型携带者（原文此处存在重复输入的<i>p</i>笔误，已按语义修正）。饥饿感评分处于最低四分位组的患者，其EBMIL较最高四分位组患者高出32%（<i>p</i> <b>研究结论：</b> <i>LYPLAL1</i>基因基因型与RYGB术后患者的饮食行为差异及体质量大幅丢失情况显著相关。对患者进行基因分型并结合饮食行为相关问卷评估，或可辅助预测RYGB手术的治疗成功率。