Association of cystic fibrosis transmembrane conductance regulator (CFTR) mutation/variant/haplotype and tumor necrosis factor (TNF) promoter polymorphism in hyperlipidemic pancreatitis
Association of cystic fibrosis transmembrane conductance regulator (CFTR) mutation/variant/haplotype and tumor necrosis factor (TNF) promoter polymorphism in hyperlipidemic pancreatitis
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DOI：
10.1373/clinchem.2007.093492
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发表时间：
2008-01-01
影响因子：
9.3
通讯作者：
Wong, Jau-Min
中科院分区：
文献类型：
--
作者：
Chang, Yu-Ting;Chang, Ming-Chu;Wong, Jau-Min
背景：高甘油三酯血症（HTG）导致胰腺炎的机制尚不清楚。我们试图确定是否有基因参与胰腺导管或腺泡细胞损伤，包括阳离子胰蛋白酶原基因[蛋白酶，丝氨酸，（胰蛋白酶1）（PRSS 1）]、胰腺分泌性胰蛋白酶抑制剂基因[丝氨酸肽酶抑制剂，Kazal I型（SPINK 1）]、囊性纤维化跨膜传导调节因子基因[囊性纤维化跨膜传导调节因子（ATP结合盒亚家族C，成员7）（CFTR）]和炎症基因如肿瘤坏死因子[肿瘤坏死因子，TNF超家族，成员2（TNF）]与HTG患者的高脂血症性胰腺炎（HLP）相关。我们对台湾126例HTG患者（46例HLP和80例无HLP）进行了遗传分析。通过异源双链分析技术鉴定了PRSS 1、SPINK 1和CFTR基因的整个编码区和内含子区，并通过测序分析进行了确认。125 G/C、1001 + IIC>T、1540 A>G的存在CFTR中2694 T>G和4521 G>A，SPINK 1中272 C>T的存在，以及TNF启动子多态性通过直接测序测量CFTR（核苷酸位置1031、863、857、308和308）dCFTR：在126名HTG患者中，13名（10.3%）携带CFTR突变。在我们的患者或HTG对照中未检测到PRSS 1或SPINK 1突变。HTG伴HLP组CFTR基因突变率为26.1%（12/46），HTG不伴HLP组CFTR基因突变率为1.3%（1/80），差异有显著性（P
BACKGROUND: The mechanism by which hypertriglyceridemia (HTG) leads to pancreatitis is not clear. We sought to determine whether the genes involved in pancreatic ductal or acinar cell injury, including the cationic trypsinogen gene [protease, serine, 1 (trypsin 1) (PRSS1)], the pancreatic secretory trypsin inhibitor gene [serine peptidase inhibitor, Kazal type I (SPINK1)], the cystic fibrosis transmembrane conductance regulator gene [cystic fibrosis transmembrane conductance regulator (ATP-binding cassette subfamily C, member 7) (CFTR)], and inflammation genes such as tumor necrosis factor [tumor necrosis factor, TNF superfamily, member 2 (TNF)] are associated with hyperlipidemic pancreatitis (HLP) in patients with HTG.METHODS: We performed genetic analysis of 126 HTG patients in Taiwan (46 with HLP and 80 without HLP). The entire coding and intronic regions of the PRSS1, SPINK1, and CFTR genes were identified by heteroduplex analysis techniques and were confirmed by sequencing analysis. The presence of 125G/C, 1001 + IIC>T, 1540A>G (Met470Val), 2694T>G, and 4521G>A in CFTR, the presence of 272C>T in SPINK1, and TNF promoter polymorphisms (nucleotide positions 1031, 863, 857, 308, and 308) were measured by direct sequencing.RESULTs: Of the 126 HTG patients, 13 (10.3%) carried a CFTR mutation. No PRSS1 or SPINK1 mutations were detected in our patients or in HTG controls. The CFTR gene mutation rates in HTG with and without HLP were 26.1% (12 of 46) and 1.3% (1 of 80), respectively (P