Precision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Charlton 8-142, 200 First St. S.W, Rochester, MN, 55902, USA.
Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
Obes Surg. 2022 Aug;32(8):2632-2640. doi: 10.1007/s11695-022-06122-9. Epub 2022 Jun 3.
Heterozygous variants in the leptin-melanocortin pathway are associated with obesity. However, their effect on the long-term outcomes after Roux-en-Y gastric bypass (RYGB) is still unknown.
In this matched case-control study, 701 participants from the Mayo Clinic Biobank with a history of RYGB were genotyped. Sixty-three patients had a heterozygous variant in the leptin-melanocortin pathway. After excluding patients with potential confounders, carriers were randomly matched (on sex, age, body mass index [BMI], and years since surgery) with two non-carrier controls. The electronic medical record of carriers and matched non-carriers was reviewed for up to 15 years after RYGB.
A total of 50 carriers and 100 matched non-carriers with a history of RYGB were included in the study. Seven different genes (LEPR, PCSK1, POMC, SH2B1, SRC1, MC4R, and SIM1) in the leptin-melanocortin pathway were identified. At the time of surgery, the mean age was 50.8 ± 10.6 years, BMI 45.6 ± 7.3 kg/m, and 79% women. There were no differences in postoperative years of follow-up, Roux limb length, or gastric pouch size between groups. Fifteen years after RYGB, the percentage of total body weight loss (%TBWL) in carriers was - 16.6 ± 10.7 compared with - 28.7 ± 12.9 in non-carriers (diff = 12.1%; 95% CI, 4.8 to 19.3) and the percentage of weight regain after maximum weight loss was 52.7 ± 29.7 in carriers compared with 29.8 ± 20.7 in non-carriers (diff = 22.9%; 95% CI, 5.3 to 40.5). The nadir %TBWL was lower - 32.1 ± 8.1 in carriers compared with - 36.8 ± 10.4 in non-carriers (diff = 4.8%; 95% CI 1.8 to 7.8).
Carriers of a heterozygous variant in the leptin-melanocortin pathway have a progressive and significant weight regain in the mid- and long-term after RYGB. Genotyping patients experiencing significant weight regain after RYGB could help implement multidisciplinary and individualized weight loss interventions to improve weight maintenance after surgery.
瘦素-黑素皮质素途径中的杂合变体与肥胖有关。然而，它们对 Roux-en-Y 胃旁路术（RYGB）后的长期结果的影响仍不清楚。
在这项匹配的病例对照研究中，对来自梅奥诊所生物库的 701 名有 RYGB 病史的参与者进行了基因分型。63 名患者在瘦素-黑素皮质素途径中存在杂合变体。排除潜在混杂因素的患者后，携带者随机与两名非携带者对照（按性别、年龄、体重指数 [BMI] 和手术后年限）匹配。对携带者和匹配的非携带者的电子病历进行了长达 15 年的 RYGB 后随访。
共有 50 名携带杂合变体和 100 名匹配的非携带者纳入研究。在瘦素-黑素皮质素途径中确定了 7 个不同的基因（LEPR、PCSK1、POMC、SH2B1、SRC1、MC4R 和 SIM1）。手术时，平均年龄为 50.8 ± 10.6 岁，BMI 为 45.6 ± 7.3kg/m，79%为女性。两组间术后随访年限、Roux 肢体长度或胃囊大小无差异。在 RYGB 后 15 年，携带者的总体重减轻百分比（%TBWL）为-16.6 ± 10.7，而非携带者为-28.7 ± 12.9（差值为 12.1%；95%CI，4.8 至 19.3），最大体重减轻后体重恢复百分比在携带者中为 52.7 ± 29.7，而非携带者中为 29.8 ± 20.7（差值为 22.9%；95%CI，5.3 至 40.5）。携带者的最低%TBWL 为-32.1 ± 8.1，而非携带者为-36.8 ± 10.4（差值为 4.8%；95%CI，1.8 至 7.8）。
瘦素-黑素皮质素途径杂合变体携带者在 RYGB 后的中远期体重明显增加。对 RYGB 后体重明显增加的患者进行基因分型，有助于实施多学科和个体化的减肥干预措施，以改善手术后的体重维持。
