SPINK1 Promoter Variants in Chronic Pancreatitis

被引：14

作者：

Hegyi, Eszter ^{[1
,2
]}

Geisz, Andrea ^{[1
,3
]}

Sahin-Toth, Miklos ^{[3
]}

Derikx, Monique H. M. ^{[3
]}

Nemeth, Balazs Csaba ^{[3
]}

Balazs, Anita ^{[1
]}

Hritz, Istvan ^{[1
]}

Izbeki, Ferenc ^{[4
]}

Halasz, Adrienn ^{[4
]}

Parniczky, Andrea ^{[5
]}

Takacs, Tamas ^{[1
]}

Kelemen, Dezso ^{[6
]}

Sarlos, Patricia ^{[7
]}

Hegyi, Peter ^{[8
]}

Czako, Laszlo ^{[1
]}

机构：

[1] Univ Szeged, Dept Med 1, Koranyi Fasor 8-10, H-6720 Szeged, Hungary

[2] Comenius Univ, Sch Med, Dept Pediat 2, Univ Childrens Hosp, Bratislava, Slovakia

[3] Boston Univ, Dept Mol & Cell Biol, Henry M Goldman Sch Dent Med, Boston, MA 02215 USA

[4] Szent Gyorgy Teaching Hosp Cty Fejer, Dept Med 1, Szekesfehervar, Hungary

[5] Heim Pal Childrens Hosp, Budapest, Hungary

[6] Univ Pecs, Dept Surg, Pecs, Hungary

[7] Univ Pecs, Dept Internal Med 1, Pecs, Hungary

[8] MTA SZTE Translat Gastroenterol Res Grp, Szeged, Hungary

来源：

PANCREAS | 2016年 / 45卷 / 01期

基金：

匈牙利科学研究基金会;

关键词：

chronic pancreatitis; SPINK1 promoter region; luciferase reporter gene assay; INHIBITOR PSTI GENE; SERINE-PROTEASE INHIBITOR; CATIONIC TRYPSINOGEN GENE; FUNCTIONAL-ANALYSIS; MISSENSE MUTATIONS; HEREDITARY PANCREATITIS; JAPANESE PATIENTS; KAZAL TYPE-1; CFTR; PRSS1;

D O I：

10.1097/MPA.0000000000000412

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Objectives Serine protease inhibitor Kazal type 1 (SPINK1) provides an important line of defense against premature trypsinogen activation within the pancreas. Our aim was to identify pathogenic SPINK1 promoter variants associated with chronic pancreatitis (CP). Methods One hundred CP patients (cases) and 100 controls with no pancreatic disease from the Hungarian National Pancreas Registry were enrolled. Direct sequencing of SPINK1 promoter region was performed. Functional characterization of variants was carried out using luciferase reporter gene assay. Results Two common polymorphisms (c.-253T>C and c.-807C>T) were found in both cases and controls. Variant c.253T>C was enriched in cases relative to controls (odds ratio, 2.1; 95% confidence interval, 1.2-3.8; P = 0.015). Variant c.-215G>A was detected in 3 of 100 cases; always linked with the pathogenic variant c.194+2T>C. Novel promoter variants c.-14G>A, c.-108G>T, and c.-246A>G were identified in 1 case each. Functional analysis showed decreased promoter activity for variants c.-14G>A (80%), c.-108G>T (31%), and c.-246A>G (47%) whereas activity of variant c.-215G>A was increased (201%) and variant c.-253T>C was unchanged compared with wild type. Conclusions The common promoter variant c.-253T>C was associated with CP in this cohort. Two of 3 newly identified SPINK1 promoter variants seem to exhibit significant functional defects and should be considered potential risk factors for CP.

引用

页码：148 / 153

页数：6

共 45 条

[1] Pathways to Injury in Chronic Pancreatitis: Decoding the Role of the High-Risk SPINK1 N34S Haplotype Using Meta-Analysis [J].