Differential roles of the SPINK1 gene mutations in alcoholic and nonalcoholic chronic pancreatitis
Differential roles of the SPINK1 gene mutations in alcoholic and nonalcoholic chronic pancreatitis
复制标题
DOI：
10.1007/s00535-006-1921-z
复制
发表时间：
2007-01-01
影响因子：
6.3
通讯作者：
Shimosegawa, Tooru
中科院分区：
文献类型：
--
作者：
Masamune, Atsushi;Kume, Kiyoshi;Shimosegawa, Tooru
背景慢性胰腺炎（CP）的危险因素除了酒精外，在很大程度上是未知的。识别环境和遗传危险因素对CP的早期诊断非常重要。我们在这里研究了丝氨酸蛋白酶抑制剂Kazal I型（SPINKI）基因突变在日本CP患者中的患病率，以及突变阳性和阴性患者的病程是否不同。方法.从96名CP患者和165名健康对照中制备基因组DNA。PCR扩增SPINKI基因的所有外显子和启动子区，并直接测序。回顾了患者的临床病程。结果家族性和特发性CP患者[N34 S; IVS 1 - 37 T> C]和[-215 G> A; IVS 3 + 2 T> C]突变的患病率分别为55.6%和11.1%，高于对照组（0.6%和0%）。N34 S和IVS 3 + 2 T> C突变在酒精性CP患者中的检出率分别为0%和4.5%（P < 0.05）。与没有SPINKI突变的患者相比，N34 S突变的患者表现出更早的症状发作和更多的主胰管扩张，其次是更频繁的手术和/或内镜干预以及胰腺癌的发展。结论. SPINKI突变与特发性和家族性CP相关，而在酒精性CP中的作用不太明显。具有N34 S突变的患者表现出更严重的临床病程，这意味着遗传风险评估可能有助于识别可能发展为严重CP的个体，并允许有针对性地关注减缓或预防疾病进展。
Background. Risk factors for chronic pancreatitis (CP) are largely unknown except for alcohol. Identification of environmental and genetic risk factors is important for the early diagnosis of CP. We here examined the prevalence of the serine protease inhibitor Kazal type I (SPINKI) gene mutations in Japanese patients with CP, and whether the disease course was different between mutation-positive and -negative patients. Methods. Genomic DNA was prepared from 96 CP patients and 165 healthy controls. All exons and the promoter region of the SPINKI gene were amplified by polymerase chain reaction, and directly sequenced. Clinical courses of the patients were reviewed. Results. The prevalence of [N34S; IVS1-37T > C] and [-215G > A; IVS3+2T > C] mutations was higher in patients with familial (55.6% and 11.1%, respectively) and idiopathic (15.2% and 18.1%) CP than in controls (0.6% and 0%). The N34S and IVS3+2T > C mutations were present in 0% and 4.5% (P < 0.05 vs control) of patients with alcoholic CP. Patients with the N34S mutation presented with earlier symptom onset and more dilatation of the main pancreatic duct, followed by more frequent surgical and/or endoscopic intervention and pancreatic cancer development than those without SPINKI mutations. Conclusions. SPINKI mutations were associated with idiopathic and familial CP, whereas the contribution was less evident in alcoholic CP. Patients with the N34S mutation presented more severe clinical courses, implying that genetic risk assessment might be useful to identify individuals who are likely to develop severe CP, and allow targeted attention to slow or prevent disease progression.