非酒精性脂肪性肝病、代谢综合征与含patatin样磷脂酶结构域蛋白3基因变异体

Non-alcoholic fatty liver disease, metabolic syndrome and patatin-like phospholipase domain-containing protein3 gene variants.

作者信息

Del Ben M, Polimeni L, Brancorsini M, Di Costanzo A, D'Erasmo L, Baratta F, Loffredo L, Pastori D, Pignatelli P, Violi F, Arca M, Angelico F

机构信息

Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy.

Department of Public Health and Infectious Disease, Sapienza University, Rome, Italy.

出版信息

Eur J Intern Med. 2014 Jul;25(6):566-70. doi: 10.1016/j.ejim.2014.05.012. Epub 2014 Jun 16.

DOI:10.1016/j.ejim.2014.05.012

PMID:24947770

Abstract

BACKGROUND & AIMS: Non-alcoholic fatty liver disease was traditionally interpreted as a condition which may progress to liver-related complications. However, the increased mortality is primarily a result of cardiovascular diseases. It has been suggested that fatty liver can be considered as the hepatic consequence of the metabolic syndrome. The aim was to describe the different clinical presentations of non-alcoholic fatty liver disease on the basis of the patatin-like phospholipase domain-containing protein3 (PNPLA3) rs738409 gene variant.

METHODS

Fatty liver was defined by ultrasonographic Hamaguchi's criteria in 211 consecutive subjects with non-alcoholic fatty liver disease. The rs738409 polymorphism was determined by TaqMan assays. Metabolic syndrome was defined according to ATPIII modified criteria.

RESULTS

Prevalence of PNPLA3-148II, PNPLA3-148IM, and PNPLA3-148MM genotypes was 45.0%, 40.7%, and 14.3% respectively. Prevalence of metabolic syndrome progressively increased with the severity of liver steatosis (from 52.5% to 65.2%, and 82.3% respectively, p<0.01). The PNPLA3-148MM group had significantly lower mean serum triglycerides (p<0.001), Framingham cardiovascular risk score (p<0.01) and lower prevalence of metabolic syndrome (p<0.05) and its components. Age and HOMA-IR were positive independent predictors of metabolic syndrome, while a negative independent association was found between metabolic syndrome and the homozygotes PNPLA3 I148M variant.

CONCLUSIONS

We suggest a lower prevalence of MetS and reduced cardiovascular risk in NAFLD patients with PNPLA3MM genotype.

摘要

背景与目的

非酒精性脂肪性肝病传统上被认为是一种可能进展为肝脏相关并发症的疾病。然而，死亡率增加主要是心血管疾病所致。有人提出，脂肪肝可被视为代谢综合征的肝脏表现。目的是基于含帕他汀样磷脂酶结构域蛋白3（PNPLA3）rs738409基因变异描述非酒精性脂肪性肝病的不同临床表现。

方法

采用超声检查的滨口标准对211例连续性非酒精性脂肪性肝病患者进行脂肪肝的定义。通过TaqMan分析法确定rs738409多态性。代谢综合征根据ATPIII修订标准进行定义。

结果

PNPLA3 - 148II、PNPLA3 - 148IM和PNPLA3 - 148MM基因型的患病率分别为45.0%、40.7%和14.3%。代谢综合征的患病率随肝脏脂肪变性严重程度逐渐增加（分别从52.5%增至65.2%和82.3%，p<0.01）。PNPLA3 - 148MM组的平均血清甘油三酯显著更低（p<0.001），弗雷明汉姆心血管风险评分更低（p<0.01），代谢综合征及其组分的患病率更低（p<0.05）。年龄和HOMA - IR是代谢综合征的阳性独立预测因素，而代谢综合征与纯合子PNPLA3 I148M变异之间存在负向独立关联。