基因君官网
2015年1月12日 讯 /生物谷BIOON/ –近日，一项发表于国际杂志Clinical and Translational Gastroenterology上的研究论文中，来自匹兹堡大学的研究人员通过研究发现，遗传突变、吸烟以及饮酒可相互作用共同增加个体患慢性胰腺炎的风险，相关研究或可揭示为何某些个体会患慢性胰腺炎，而单独的重度吸烟或重度饮酒者却并无疾病表现。
研究者David Whitcomb解释道，疾病的发病过程开始于急性胰腺炎，炎性症状的起初表现为恶心、呕吐以及上腹部严重疼痛，有时候会出现放射痛，这或许都是由过度饮酒及胆囊问题所致；目前三分之一的病人会有反复发作的急性胰腺炎，而三分之一的患者则会引发慢性胰腺炎，最终胰腺因炎性结痂。
吸烟和饮酒被认为是引发慢性胰腺炎的强风险因子，但并不是每个吸烟或饮酒者都会损伤其胰腺组织，本文研究还发现了一些遗传突变，当其同生活方式的风险因子相结合或许就会使得个体对慢性胰腺炎更加易感。
文章中，研究者对100多名慢性胰腺炎或复发性急性胰腺炎患者进行研究，评估了患者机体的基因特性以及其饮酒、吸烟的习惯，同时以健康志愿者作为对照；结果研究人员发现了一种名为CTRC的基因，其可以通过使胰蛋白酶过早活化来保护胰腺细胞免于损伤，胰蛋白酶是胰腺中的一种消化酶。
研究者发现，CTRC基因的特定突变是饮酒和吸烟相关的慢性胰腺炎发生的风险因子，大约10%的高加索人机体中都携带有该基因突变；研究者推测有可能是这种基因突变后，就失去了保护胰腺的功能。最后研究者Whitcomb指出，当人们因急性胰腺炎入院治疗时，我们往往会进行基因突变的检查，并且尽一切可能来帮助他们戒烟及戒酒，同时检测我们的疗法是否有效。（生物谷Bioon.com）
本文系生物谷原创编译整理，欢迎转载！转载请注明来源并附原文链接。谢谢！
The Common Chymotrypsinogen C (CTRC) Variant G60G (C.180T) Increases Risk of Chronic Pancreatitis But Not Recurrent Acute Pancreatitis in a North American Population
Jessica LaRusch1,5, Antonio Lozano-Leon1,6, Kimberly Stello1, Amanda Moore1,7, Venkata Muddana1,8, Michael O’Connell1, Brenda Diergaarde2, Dhiraj Yadav1 and David C Whitcomb1,3,4 for the NAPS2 Consortium9
OBJECTIVES: Recurrent acute pancreatitis (RAP) is a complex inflammatory disorder that may progress to fibrosis and other irreversible features recognized as chronic pancreatitis (CP). Chymotrypsinogen C (CTRC) protects the pancreas by degrading prematurely activated trypsinogen. Rare mutations are associated with CP in Europe and Asia. We evaluated the occurrence of CTRC variants in subjects with RAP, CP, and controls from the North American Pancreatitis Study II cohort. METHODS: CP (n=694), RAP (n=448), and controls (n=1017) of European ancestry were evaluated. Subgroup analysis included CFTR and SPINK1 variants, alcohol, and smoking. RESULTS: We identified previously reported rare pathogenic CTRC A73T, R254W, and K247_R254del variants, intronic variants, and G60G (c.180 C>T; rs497078). Compared with controls (minor allele frequency (MAF)=10.8%), c.180T was associated with CP (MAF=16.8%, P<0.00001) but not RAP (MAF=11.9% P=NS). Trend test indicated co-dominant risk for CP (CT odds ratio (OR)=1.36, 95% confidence interval (CI)=1.13–1.64, P=0.0014; TT OR=3.98, 95% CI=2.10–7.56, P<0.0001). The T allele was significantly more frequent with concurrent pathogenic CFTR variants and/or SPINK1 N34S (combined 22.9% vs. 16.1%, OR 1.92, 95% C.I. 1.26–2.94, P=0.0023) and with alcoholic vs. non-alcoholic CP etiologies (20.8% vs. 12.4%, OR=1.9, 95% CI=1.30–2.79, P=0.0009). Alcohol and smoking generally occurred together, but the frequency of CTRC c.180 T in CP, but not RAP, was higher among never drinkers–ever smokers (22.2%) than ever drinker–never smokers (10.8%), suggesting that smoking rather than alcohol may be the driving factor in this association. CONCLUSIONS: The common CTRC variant c.180T acts as disease modifier that promotes progression from RAP to CP, especially in patients with CFTR or SPINK1 variants, alcohol, or smoking.