Keratin 8 sequence variants in patients with pancreatitis and pancreatic cancer
Keratin 8 sequence variants in patients with pancreatitis and pancreatic cancer
复制标题
胰腺炎和胰腺癌患者的角蛋白 8 序列变异
DOI：
10.1007/s00109-006-0096-7
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
H. Witt
中科院分区：
文献类型：
--
作者：
M. Treiber;H. Schulz;O. Landt;J. Drenth;C. Castellani;F. Real;N. Akar;R. Ammann;M. Bargetzi;E. Bhatia;A. Demaine;Cinzia Battagia;A. Kingsnorth;D. O’reilly;K. Truninger;M. Koudova;J. Spicak;M. Černý;H. Menzel;P. Moral;P. Pignatti;M. Romanelli;O. Rickards;G. D. De Stefano;N. Zarnescu;G. Choudhuri;S. Sikora;J. Jansen;F. Weiss;M. Pietschmann;N. Teich;T. Gress;J. Ockenga;H. Schmidt;A. Kage;J. Halangk;J. Rosendahl;D. Groneberg;R. Nickel;H. Witt
角蛋白8（KRT 8）是胃肠道单层上皮细胞中表达的主要中间丝蛋白之一。过表达人KRT 8的转基因小鼠表现出胰腺单核细胞浸润、间质纤维化和腺泡细胞发育不良，导致胰腺外分泌功能不全。这些实验数据与最近描述KRT 8变异与慢性胰腺炎之间的关联的报告一致。这促使我们研究胰腺疾病患者中的KRT 8多态性。在患有各种病因的急性和慢性胰腺炎或胰腺癌的患者队列中评估KRT 8 Y 54 H和G62 C多态性，这些患者来自奥地利（n=16）、捷克共和国（n=90）、德国（n=1698）、英国（n=36）、印度（n=60）、意大利（n=143）、荷兰（n=128）、罗马尼亚（n=3）、西班牙（n=133）和瑞士（n=129）。我们还研究了来自这些国家的4,234名对照受试者和来自贝宁、喀麦隆、埃塞俄比亚、厄瓜多尔和土耳其的1,492名对照受试者。通过荧光共振能量转移探针的熔解曲线分析来分析多态性。G62 C的频率在急性或慢性胰腺炎、胰腺癌患者和对照个体之间没有差异。欧洲人群中G62 C的频率从0.4%到3.8%不等，呈西北向东南下降趋势。在2，436名患者中没有检测到Y 54 H改变。只有3/4，580（0.07%）的欧洲、土耳其和印度对照受试者为Y 54 H杂合子，而非洲裔对照受试者为34/951（3.6%）。我们的数据表明，KRT 8的改变，Y 54 H和G62 C，不倾向于患者的胰腺炎或胰腺癌的发展。
Keratin 8 (KRT8) is one of the major intermediate filament proteins expressed in single-layered epithelia of the gastrointestinal tract. Transgenic mice over-expressing human KRT8 display pancreatic mononuclear infiltration, interstitial fibrosis and dysplasia of acinar cells resulting in exocrine pancreatic insufficiency. These experimental data are in accordance with a recent report describing an association between KRT8 variations and chronic pancreatitis. This prompted us to investigate KRT8 polymorphisms in patients with pancreatic disorders. The KRT8 Y54H and G62C polymorphisms were assessed in a cohort of patients with acute and chronic pancreatitis of various aetiologies or pancreatic cancer originating from Austria (n=16), the Czech Republic (n=90), Germany (n=1698), Great Britain (n=36), India (n=60), Italy (n=143), the Netherlands (n=128), Romania (n=3), Spain (n=133), and Switzerland (n=129). We also studied 4,234 control subjects from these countries and 1,492 control subjects originating from Benin, Cameroon, Ethiopia, Ecuador, and Turkey. Polymorphisms were analysed by melting curve analysis with fluorescence resonance energy transfer probes. The frequency of G62C did not differ between patients with acute or chronic pancreatitis, pancreatic adenocarcinoma and control individuals. The frequency of G62C varied in European populations from 0.4 to 3.8%, showing a northwest to southeast decline. The Y54H alteration was not detected in any of the 2,436 patients. Only 3/4,580 (0.07%) European, Turkish and Indian control subjects were heterozygous for Y54H in contrast to 34/951 (3.6%) control subjects of African descent. Our data suggest that the KRT8 alterations, Y54H and G62C, do not predispose patients to the development of pancreatitis or pancreatic cancer.
影响因子：
158.5
作者：
Cohn, JA;Friedman, KJ;Jowell, PS
通讯作者：
Jowell, PS
影响因子：
10.5
作者：
BARIBAULT, H;PRICE, J;OSHIMA, RG
通讯作者：
OSHIMA, RG