Association study between single nucleotide polymorphisms of UGT1 A1 with NAFLD and serum lipids in children

Abstract

Objective To investigate the associations between single nucleotide polymorphisms of UDP glucuronosyltransferase Family 1 Member A1 ( UGT1 A1) with non-alcoholic fatty liver disease (NAFLD) and levels of serum lipids in Beijing children, and to provide scientific evidence for the study of genetic mechanism.

Methods In total, 1 027 children aged 7–18 years were recruited from two primary schools and three middle schools from Haidian district of Beijing, who were randomly assigned to case group ( n = 162) and control group ( n = 865). General condition and medical history were collected by trained field health workers. Height, weight and liver ultrasound were examined. Additionally, fasting venous blood were collected to detect serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL–C), high density lipoprotein cholesterol (HDL–C) and alanine aminotransferase (ALT). The single nucleotide polymorphisms (SNPs) of UGT1 A1 were genotyped. Binary logistic regression and multiple linear regression were applied to analyze the associations between three SNPs of UGT1 A1 and NAFLD, ALT and levels of serum lipids.

Results The SNP rs10929303 (C>T) of UGT1 A1 was negatively associated with NAFLD ( OR = 0.51, 95% CI = 0.32-0.83, P = 0.01), while the SNP rs4148323 (G>A) was negatively associated with the serum level of TC ( B = −0.10, 95% CI = −0.19–−0.02, P = 0.02); in addition, results were consistent regardless of whether the TC level was measured using a categorical variable or continuous variable.

Conclusion The SNP rs10929303 of UGT1 A1 is associated with NAFLD, and the SNP rs4148323 of UGT1 A1 is associated with TC levels in Beijing children.

Abstract

【摘要】 目的 探讨尿苷二磷酸葡萄糖醛酸转移酶 1A1 ( UGT1 A1) 基因的单核苷酸多态性 (SNPs) 与儿童青少年非酒精性 脂肪性肝病 (non-alcoholic fatty liver disease, NAFLD) 和血脂水平的关系, 为 NAFLD 的遗传机制研究提供科学依据。 方法 2006—2007 年在北京市海淀区 3 所中学和 2 所小学中选取 1 027 名 7~18 岁儿童青少年为研究对象, 分病例组 (患 NAFLD 的学生 162 名) 与对照组 (非 NAFLD 学生 865 名), 由专职人员记录学生一般情况和既往病史, 测量身高、体重, 进行肝脏 B 超检查, 并采集清晨空腹静脉血, 测定血清总胆固醇 (TC)、三酰甘油 (TG)、高密度脂蛋白胆固醇 (HDL-C)、低密度脂蛋白 胆固醇 (LDL-C) 和丙氨酸氨基转移酶 (ALT) 水平。对 UGT1 A1 基因 SNPs 进行分型, 分别采用二分类 Logistic 回归和多元 线性回归分析 UGT1 A1 基因 3 个 SNPs 与 NAFLD 和谷丙转氨酶 (ALT) 及血脂水平的关系。 结果 UGT1 A1 基因 rs10929303 位点 T 等位基因与 NAFLD 的发生存在负相关 ( OR = 0.51, 95% CI= 0.32~0.83, P = 0.01)。 rs4148323 位点 A 等 位基因与 TC 水平呈负相关 ( B = −0.10, 95% CI = −0.19~−0.02, P = 0.02); 将 TC 水平作分类变量进行分析时, 结果与将其 作为连续性变量分析类似。 结论 UGT1 A1 基因 rs10929303 位点多态性与儿童青少年 NAFLD 相关, 且 rs4148323 位点多态 性和 TC 水平相关。