The-159C/T polymorphism in the promoter region of the CD14 gene is associated with advanced liver disease and higher serum levels of acute-phase proteins in heavy drinkers
The-159C/T polymorphism in the promoter region of the CD14 gene is associated with advanced liver disease and higher serum levels of acute-phase proteins in heavy drinkers
复制标题
DOI：
10.1097/01.alc.0000171977.25531.7a
复制
发表时间：
2005-07-01
影响因子：
3.2
通讯作者：
Vidal, C
中科院分区：
文献类型：
--
作者：
Campos, J;Gonzalez-Quintela, A;Vidal, C
背景：对内毒素（脂多糖）的先天炎症反应有助于酒精性肝病（ALD）的发展。 CD14（一种脂多糖受体）基因启动子区的单核苷酸多态性（-159C/T）可能与 ALD 的发生有关。我们还试图研究重度饮酒者的CD14/-159C/T多态性与晚期ALD和急性期蛋白水平之间的关系。方法：对连续入院内科的138名重度饮酒者进行CD14/-159C/T多态性基因分型。分析血清样本的脂多糖结合蛋白 (LBP)、可溶性 CD14 (sCD14)、C 反应蛋白 (CRP) 和免疫球蛋白 (Ig) A、IgG 和 IgM。腹水或肝性脑病患者 (n = 35) 被归类为晚期 ALD。 结果：调整潜在混杂变量后，CD14/-159TT 基因型与晚期 ALD 呈正相关（比值比，2.99；95% 置信区间，1.09 - 8.24，p = 0.03）和血清 LBP（p = 0.01）和sCD14 (p = 0.04) 水平。 CD141-159CIT 多态性与 CRP、IgA、IgG 或 IgM 的血清水平无关。结论：我们的结果支持这样的观点：CD14/-159TT 纯合重度饮酒者比 CD141-159C 等位基因携带者具有更高水平的 LPS 结合急性期蛋白（LBP 和 sCD14）。此外，CD14/-159TT 基因型可能是晚期 ALD 的危险因素。
Background: Innate inflammatory responses to endotoxin (lipopolysaccharide) contribute to the development of alcoholic liver disease (ALD). A single-nucleotide polymorphism (-159C/T) in the promoter region of the gene coding for CD14 (a lipopolysaccharicle receptor) could be associated with the development of ALD. We sought too investigate the relationship between the CD14/-159C/T polymorphism and advanced ALD and acute-phase protein levels in heavy drinkers.Methods: A total of 138 heavy drinkers consecutively admitted to an Internal Medicine department were genotyped for the CD14/-159C/T polymorphism. Serum samples were analyzed for lipopolysaccharide-binding protein (LBP), soluble CD14 (sCD14), C-reactive protein (CRP), and immunoglobulin (Ig) A, IgG, and IgM. Patients with ascites or liver encephalopathy (n = 35) were classified as having advanced ALD.Results: After adjusting for potential confounding variables, the CD14/-159TT genotype was positively associated with advanced ALD (odds ratio, 2.99; 95 % confidence interval, 1.09 - 8.24, p = 0.03) and serum LBP (p = 0.01) and sCD14 (p = 0.04) levels. The CD141-159CIT polymorphism was not associated with serum levels of CRP, IgA, IgG, or IgM.Conclusions: Our results support the notion that CD14/-159TT homozygous heavy drinkers have higher levels of the LPS-binding acute-phase proteins (LBP and sCD14) than do carriers of the CD141-159C allele. Also, the CD14/-159TT genotype may be a risk factor for advanced ALD.