Variations of ABCB4 and ABCB11 genes are associated with primary intrahepatic stones
Variations of ABCB4 and ABCB11 genes are associated with primary intrahepatic stones
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ABCB4和ABCB11基因的变异与原发性肝内结石相关
DOI：
10.3892/mmr.2014.2645
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发表时间：
2015-01-01
影响因子：
3.4
通讯作者：
Li, Zhihua
中科院分区：
文献类型：
--
作者：
Pan, Shuguang;Li, Xiaowu;Li, Zhihua
ABCB 4和ABCB 11基因的变异影响胆汁的组成，并与胆汁淤积和胆石症有关。然而，它们在原发性肝内结石（PIS）形成中的作用仍有待阐明。本研究的目的是确定PIS和这些基因的变异之间是否存在关联。对176例PIS患者和178例健康人的ABCB 4和ABCB 11基因进行外显子测序分析。在23例PIS杂合子患者中，发现ABCB 4基因的一个突变（69233，G>A）和ABCB 11基因的另外两个突变（参考单核苷酸多态性（rs）118109635和rs497692）与PIS相关（在ABCB 4基因第26外显子检测到PA）。在健康个体或单核苷酸多态性数据库中未检测到该突变。ABCB 4中的No.69233 G>A与蛋白表达改变无关，但与PIS复发率降低相关（P=0.01）。错义突变rs118109635位于ABCB 11的第21外显子，与ABCB 11蛋白表达增加（P=0.032）以及改变胆盐输出泵功能相关。据报道，外显子24中的另一个同义突变rs497692降低ABCB11蛋白表达（P=0.001）。此外，ABCB 11基因突变与术前黄疸有关（P
Variations of the ABCB4 and ABCB11 genes affect the composition of bile and are associated with cholestasis and cholelithiasis. However, their roles in the formation of primary intrahepatic stones (PIS) remains to be elucidated. The aim of the present study was to determine whether there is an association between PIS and variations in these genes. Exon sequencing was performed in order to analyze the ABCB4 and ABCB11 genes of 176 patients with PIS and 178 healthy subjects. One mutation in ABCB4 (no. 69233, G>A) and two other mutations in ABCB11, reference single nucleotide polymorphism (rs)118109635 and rs497692, were identified in association with PIS (PA was detected in exon 26 of ABCB4 in 23 heterozygous patients with PIS. This mutation was not detected in healthy individuals or in the Single Nucleotide Polymorphism Database. No. 69233 G>A in ABCB4 was not associated with altered protein expression but with a reduced rate of PIS recurrence (P=0.01). The missense mutation rs118109635 was located on exon 21 of ABCB11 and was associated with the increased expression of ABCB11 protein (P=0.032) as well as altered bile salt export pump function. Another synonymous mutation, rs497692 in exon 24 was reported to decrease ABCB11 protein expression (P=0.001). In addition, the mutations of ABCB11 were associated with preoperative jaundice (P