Männistö Ville T, Kaminska Dorota, Haal Sylke, Asteljoki Juho, Luukkonen Panu K, Käkelä Pirjo, Tavaglione Federica, van Weeghel Michel, Neuvonen Mikko, Niemi Mikko, Romeo Stefano, Nieuwdorp Max, Pihlajamäki Jussi, Groen Albert K
Departments of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
Department of Experimental Vascular Medicine, Amsterdam UMC, Location AMC at University of Amsterdam, Amsterdam, The Netherlands.
Gastro Hep Adv. 2024 Mar 12;3(5):594-601. doi: 10.1016/j.gastha.2024.03.005. eCollection 2024.
Gallstone disease (GSD) associates with significant morbidity and mortality. Decreased secretion of bile acids has been suggested as a driving factor for GSD. Recently, we linked the protein phosphatase 1 regulatory subunit 3 beta ( rs4240624 genotype to decreased bile acid levels in bile. In this study, we investigated whether these individuals had an increased risk for GSD as well as the differences in the lipid composition of the gallbladder bile of these individuals compared to controls and patients with GSD.
Bile acids, cholesterol, and phospholipid levels in gallbladder bile samples were enzymatically measured in 46 patients (34 female, age 45.7 ± 9.8 years, BMI 41.3 ± 4.4 kg/m) who underwent elective laparoscopic Roux-en-Y gastric bypass. The lipidome of gallbladder bile was analyzed using high-performance liquid chromatography-mass spectrometry. Gallstone status was evaluated using abdominal ultrasonography before the surgery.
The G allele of rs4240624 was significantly associated with GSD in patients with obesity. We validated this association in the UK Biobank. Bile lipidomics demonstrated that 13 of the 17 minor lipid classes measured were higher in individuals with the G allele. The concentrations of bile acids, cholesterol, and phospholipids, as well as the cholesterol saturation index, were lower in patients with GSD than in those without gallstones. GSD had an effect similar to that of genotype on minor lipids.
The rs4240624 genotype is associated with gallstones and with changes in gallbladder bile similar to those observed in patients with gallstones, suggesting that the genotype contributes to the risk of gallstones by altering the bile lipidome.
胆结石病（GSD）与显著的发病率和死亡率相关。胆汁酸分泌减少被认为是GSD的一个驱动因素。最近，我们发现蛋白磷酸酶1调节亚基3β（PPP1R3B）的rs4240624基因型与胆汁中胆汁酸水平降低有关。在本研究中，我们调查了这些个体患GSD的风险是否增加，以及与对照组和GSD患者相比，这些个体胆囊胆汁的脂质组成差异。
对46例接受择期腹腔镜Roux-en-Y胃旁路手术的患者（34例女性，年龄45.7±9.8岁，BMI 41.3±4.4 kg/m²）的胆囊胆汁样本中的胆汁酸、胆固醇和磷脂水平进行酶法测定。使用高效液相色谱-质谱法分析胆囊胆汁的脂质组。术前通过腹部超声评估胆结石状态。
rs4240624的G等位基因与肥胖患者的GSD显著相关。我们在英国生物银行中验证了这一关联。胆汁脂质组学表明，所测量的17种次要脂质类别中有13种在携带G等位基因的个体中含量更高。GSD患者的胆汁酸、胆固醇和磷脂浓度以及胆固醇饱和指数均低于无胆结石患者。GSD对次要脂质的影响与基因型相似。
rs4240624基因型与胆结石以及胆囊胆汁变化有关，类似于在胆结石患者中观察到的情况，这表明该基因型通过改变胆汁脂质组增加了胆结石风险。
