Length of Variable Numbers of Tandem Repeats in the Carboxyl Ester Lipase (CEL) Gene May Confer Susceptibility to Alcoholic Liver Cirrhosis but Not Alcoholic Chronic Pancreatitis
Length of Variable Numbers of Tandem Repeats in the Carboxyl Ester Lipase (CEL) Gene May Confer Susceptibility to Alcoholic Liver Cirrhosis but Not Alcoholic Chronic Pancreatitis
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DOI：
10.1371/journal.pone.0165567
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发表时间：
2016-11-01
期刊：
影响因子：
3.7
通讯作者：
Rosendahl, Jonas
中科院分区：
文献类型：
--
作者：
Fjeld, Karianne;Beer, Sebastian;Rosendahl, Jonas
研究背景羧酸乙酯脂肪酶(CEL)参与脂肪酸乙酯代谢，与酒精性胰腺炎密切相关。CEL基因在第11外显子含有数量可变的串联重复序列(VNTR)区域。该VNTR的变异被认为与单基因胰腺疾病有关，而在慢性胰腺炎(CP)中的结果则相互矛盾。方法用毛细管电泳法对395例酒精性CP患者、218例酒精性肝硬变(ALC)患者和327名来自德国和英国(UK)的健康对照进行了片段长度分析。结果12个重复序列在UK ACP患者中较对照组高表达(P=0.04)，而在德国ALC患者中较酒精中毒CP患者富含12个重复序列(P=0.03)。德国ALC患者CELVNTR14和15个重复序列的频率与健康对照组相比差异有统计学意义(P分别为0.03和0.008)。然而，在vntr长度的基因分型和合并分析中，没有统计意义上的相关性。此外，UK ALC患者中16-16等位基因和16个重复序列的频率明显高于酒精性CP患者(P=0.034.0 5和0.0 2)。在所有其他计算中，包括合并的德国和英国数据，等位基因频率和基因分布在患者和对照组之间或酒精性CP和AL之间没有显著差异。结论我们没有获得CEL VNTR长度与酒精性CP相关的证据。然而，我们的结果表明CEL VNTR长度可能与ALC相关，这一发现需要在更大的队列中得到澄清。
BackgroundCarboxyl-ester lipase (CEL) contributes to fatty acid ethyl ester metabolism, which is implicated in alcoholic pancreatitis. The CEL gene harbours a variable number of tandem repeats (VNTR) region in exon 11. Variation in this VNTR has been linked to monogenic pancreatic disease, while conflicting results were reported for chronic pancreatitis (CP). Here, we aimed to investigate a potential association of CEL VNTR lengths with alcoholic CP.MethodsOverall, 395 alcoholic CP patients, 218 patients with alcoholic liver cirrhosis (ALC) serving as controls with a comparable amount of alcohol consumed, and 327 healthy controls from Germany and the United Kingdom (UK) were analysed by determination of fragment lengths by capillary electrophoresis. Allele frequencies and genotypes of different VNTR categories were compared between the groups.ResultsTwelve repeats were overrepresented in UK ACP patients (P = 0.04) compared to controls, whereas twelve repeats were enriched in German ALC compared to alcoholic CP patients (P = 0.03). Frequencies of CEL VNTR lengths of 14 and 15 repeats differed between German ALC patients and healthy controls (P = 0.03 and 0.008, respectively). However, in the genotype and pooled analysis of VNTR lengths no statistical significant association was depicted. Additionally, the 16-16 genotype as well as 16 repeats were more frequent in UK ALC than in alcoholic CP patients (P = 0.034 and 0.02, respectively). In all other calculations, including pooled German and UK data, allele frequencies and genotype distributions did not differ significantly between patients and controls or between alcoholic CP and ALC.ConclusionsWe did not obtain evidence that CEL VNTR lengths are associated with alcoholic CP. However, our results suggest that CEL VNTR lengths might associate with ALC, a finding that needs to be clarified in larger cohorts.