Acalovschi Monica, Ciocan Anca, Mostean Ofelia, Tirziu Simona, Chiorean Erica, Keppeler Hildegard, Schirin-Sokhan Ramin, Lammert Frank
3rd Medical Clinic, University of Medicine and Pharmacy Cluj-Napoca, Romania.
Eur J Intern Med. 2006 Nov;17(7):490-4. doi: 10.1016/j.ejim.2006.04.012.
The role of ABCG5 and ABCG8 genes in the determination of plasma lipid levels is currently under intensive investigation. The aim of this study was to evaluate plasma lipid levels in sibling pairs with gallstones and to assess their correlation with common gene polymorphisms in the ABCG5/ABCG8 genes.
Plasma levels of cholesterol, HDL-cholesterol, and triglycerides were measured in 68 patients belonging to 34 sibling pairs with gallstones (affected sibling pairs, mean age 56.3 years) and in 68 gallstone carriers with stone-free siblings (age/gender-matched controls in a ratio of 2:1 with the index patients of the study group). Four and one non-synonymous sequence variants in ABCG8 and ABCG5 genes, respectively, were determined in the affected sibling pairs, employing allelic discrimination with 5' nuclease assays.
Plasma triglyceride levels were higher and HDL-cholesterol levels lower in the index patients than in controls. Plasma lipid levels were correlated in the members of the affected sibling pairs. Triglyceride levels were higher in carriers of the common alleles for ABCG5 Q604E and ABCG8 D19H sequence variants, and HDL-cholesterol was lower in carriers of the common alleles for ABCG5 Q604E than in carriers of the rare alleles.
The significantly different plasma lipid levels in siblings with gallstones versus controls, as well as the correlation of plasma lipids in affected sibling pairs, confirm the genetic influence in gallstone disease. Polymorphisms in ABCG5/ABCG8 genes might contribute to the genetic variation in plasma lipid levels and in cholesterol saturation of the bile.
ABCG5和ABCG8基因在血浆脂质水平测定中的作用目前正在深入研究。本研究的目的是评估患有胆结石的同胞对的血浆脂质水平，并评估其与ABCG5/ABCG8基因常见基因多态性的相关性。
对34对患有胆结石的同胞对（受影响的同胞对，平均年龄56.3岁）中的68名患者以及68名有非结石同胞的胆结石携带者（年龄/性别匹配的对照组，与研究组的指数患者比例为2:1）测量血浆胆固醇、高密度脂蛋白胆固醇和甘油三酯水平。采用5'核酸酶分析的等位基因鉴别方法，在受影响的同胞对中确定ABCG8和ABCG5基因分别有4个和1个非同义序列变异。
指数患者的血浆甘油三酯水平高于对照组，高密度脂蛋白胆固醇水平低于对照组。受影响的同胞对成员的血浆脂质水平相关。ABCG5 Q604E和ABCG8 D19H序列变异常见等位基因携带者的甘油三酯水平较高，ABCG5 Q604E常见等位基因携带者的高密度脂蛋白胆固醇低于罕见等位基因携带者。
患有胆结石的同胞与对照组之间血浆脂质水平存在显著差异，以及受影响的同胞对中血浆脂质的相关性，证实了胆结石疾病中的遗传影响。ABCG5/ABCG8基因的多态性可能导致血浆脂质水平和胆汁胆固醇饱和度的遗传变异。
