四川地区汉族人群慢性胰腺炎糜蛋白酶C基因突变的影响因素

Mutation screening of CTRC gene and related clinical study in Han population of Sichuan

目的慢性胰腺炎(CP)是胰腺实质不可逆损伤性疾病,糜蛋白酶C(CTRC)基因改变可能与CP发病有关。文章分析四川地区汉族CP人群CTRC基因的突变情况,探讨其与临床关系。方法采集106例CP患者以及148例健康对照者外周血,提取DNA进行CTRC基因全外显子测序,并分析临床相关性。结果发现1例c.611G>A杂合错义突变; 3个单核苷酸多态性(SNP)位点改变,包括1个新的SNP位点c.40+133G>A及2个已知的SNP位点改变(rs6679763和rs555015)。c.40+133G>A和rs6679763位点突变在病例组与对照组间分布差异有统计学意义(P=0.029、P=0.011)。临床基线资料表示吸烟(P=0.042)、胆道疾病(P=0.013)、血糖(P=0.017)组间差异有统计学意义。消除混杂因素,吸烟具有组间差异性(OR=2.817,95%CI:1.016～7.811,P=0.047),rs6679763突变位点分布病例组高于对照组(OR=4.893,95%CI:1.152～20.781,P=0.031)。未发现基因位点突变与环境存在相乘交互作用。结论吸烟、胆道疾病、血糖、c.611G>A,rs6679763和c.40+133G>A位点变异可能与CP有关,考虑吸烟及rs6679763位点变异是CP的独立危险因素;并初步验证了CTRC基因SNP位点rs6679763和c.40+133G>A以及点突变位点c.611G>A是四川地区汉族人群的易感基因位点。

Objective Chronic pancreatitis （CP） is an irreversible pancreatic parenchymal disease with complicated etiology. Chymotrypsin C （ CTRC ） gene variation may be related to CP occurrence. The article analyzed the mutation of CTRC gene in Han population with CP in Sichuan, and discussed its clinical relevance. Methods Peripheral blood samples were collected from 106 patients with CP and 148 healthy controls and DNA was extracted for whole exon sequencing of CTRC gene and analysis of clinical correlation. Results One case of c.611G〉A heterozygous missense mutation and three cases of single nucleotide polymorphism （SNP） site variation were found which included one new SNP c.40＋133G〉A and two known SNPs： rs6679763 and rs555015. The variation of c.40 ＋133G〉 A and rs6679763 showed a significant difference between case group and control group （ P =0.029, P =0.011）. Clinical baseline data showed significant differences between two groups on smoking （ P =0.042）, biliary disease （ P =0.013）, and blood glucose（ P =0.017）. When the confounding factors were eliminated, we found that smoking and rs6679763 variant site were significantly associated with CP risk （OR=2.817, 95%CI： 1.016-7.811, P = 0.047 ;OR = 4.893, 95%CI： 1.152-20.781, P =0.031, respectively）. There was no multiplicative interaction between gene mutation and environment or clinical data. Conclusion Smoking, biliary disease, blood glucose, c.611G〉A mutation, rs6679763 and c.40＋133G〉A variation may be related to the occurrence of CP. Smoking and rs6679763 locus variation are independent risk factors for CP, and the CTRC gene SNP locus rs6679763 and c.40＋133G〉A and the point mutation site c.611G〉A are predisposing loci in Chinese Han population of Sichuan province.