Center for Liver Diseases at Inova Fairfax Hospital, Falls Church, VA 22042, USA.
Obes Surg. 2010 May;20(5):640-50. doi: 10.1007/s11695-010-0078-2. Epub 2010 Jan 30.
BACKGROUND/AIM: There is increasing data suggesting that African Americans with NAFLD tend to have less progressive liver disease. The aim of this study is to assess differences in the hepatic gene expression of African-American and Caucasian patients with NAFLD who had undergone bariatric surgery.
A total of 94 patients (81 NAFLD and 13 weight-matched controls with normal liver biopsy) were included. Of the entire cohort, 73 were Caucasians and 21 were African Americans. All patients were undergoing bariatric surgery. Two liver biopsies were obtained at the time of surgery. One biopsy was snap-frozen for gene expression and the other biopsy was stained for pathologic assessment. Liver biopsy confirmed that 24 patients from our cohort had NASH while 57 had only simple steatosis. Snap-frozen liver biopsy specimens of these patients were then used for the RNA extraction. cDNA probes were hybridized with customized microarray gene chips containing 5,220 relevant genes. Gene expression profiles were compared between groups using significance analysis of microarrays algorithm.
In comparison to all Caucasian patients, African-American patients had over-expression of EPB41L1, IGF2, FAH, ACSL4, FUT4, CYP3A (q values < 10(-4)). In comparison to Caucasian NAFLD patients, African-American NAFLD patients showed over-expression of EPB41L1 and ACSL4 genes. Finally, in comparison to Caucasian NASH patients, African-American NASH patients showed over-expression of GSTM 2, GSTM4 and GSTM5 as well as FH and ASCL4 genes. Some genes highlighted by this analysis, particularly cytochrome CYP3A and glutathione transferases GSTM2, 4, 5, were previously implicated in the pathogenesis of NASH.
African-American patients with biopsy-proven obesity-related NAFLD and NASH have a specific hepatic gene expression pattern that may explain their differences from Caucasian patients with NAFLD in developing progressive liver disease.
背景/目的：越来越多的数据表明，非裔美国人的非酒精性脂肪性肝病（NAFLD）往往进展性较轻。本研究旨在评估接受减肥手术的非裔美国人和白种人 NAFLD 患者肝组织基因表达的差异。
共纳入 94 例患者（81 例非酒精性脂肪性肝病和 13 例肝活检正常的体重匹配对照）。整个队列中，73 例为白种人，21 例为非裔美国人。所有患者均接受减肥手术。手术时获取两个肝活检，一个用于基因表达的快速冷冻，另一个用于病理评估。肝活检证实，我们队列中有 24 例患者患有非酒精性脂肪性肝炎（NASH），而 57 例仅患有单纯性脂肪变性。然后使用这些患者的快速冷冻肝活检标本进行 RNA 提取。cDNA 探针与包含 5220 个相关基因的定制微阵列基因芯片杂交。使用差异分析微阵列算法比较组间基因表达谱。
与所有白种人患者相比，非裔美国人患者的 EPB41L1、IGF2、FAH、ACSL4、FUT4、CYP3A（q 值<10(-4)）表达上调。与白种人非酒精性脂肪性肝病患者相比，非裔美国人非酒精性脂肪性肝病患者的 EPB41L1 和 ACSL4 基因表达上调。最后，与白种人 NASH 患者相比，非裔美国人 NASH 患者的 GSTM2、GSTM4 和 GSTM5 以及 FH 和 ASCL4 基因表达上调。该分析突出显示的一些基因，特别是细胞色素 CYP3A 和谷胱甘肽转移酶 GSTM2、4、5，先前被认为与 NASH 的发病机制有关。
经活检证实肥胖相关非酒精性脂肪性肝病和 NASH 的非裔美国患者具有特定的肝组织基因表达模式，这可能解释了他们与白种人非酒精性脂肪性肝病患者在进展性肝病方面的差异。
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