SPINK1和PRSS2基因变异在热带钙化性胰腺炎中的不同作用

Divergent roles of SPINK1 and PRSS2 variants in tropical calcific pancreatitis.

作者信息

Sundaresan Santhosh, Chacko Ashok, Dutta Amit K, Bhatia Eesh, Witt Heiko, Te Morsche René H M, Jansen Jan B M J, Drenth Joost P H

机构信息

Department of Medicine, Division of Gastroenterology and Hepatology, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands.

出版信息

Pancreatology. 2009;9(1-2):145-9. doi: 10.1159/000178885. Epub 2008 Dec 13.

DOI:10.1159/000178885

PMID:19077465

Abstract

BACKGROUND/AIMS: Tropical calcific pancreatitis (TCP) refers to a type of idiopathic pancreatitis prevalent in Asia. The trypsin inhibitor (SPINK1) N34S variant partially explains the genetic susceptibility to TCP. As anionic trypsinogen (PRSS2) G191R protects against chronic pancreatitis in Europeans, we investigated whether this variant protects from TCP in Indians.

METHODS

We enrolled 174 patients and 794 controls from two Indian tertiary care referral hospitals. We analyzed PRSS2 and SPINK1 variants by melting curve analysis, allele-specific discrimination assay, and sequencing.

RESULTS

G191R was detected in 1 TCP patient (0.6%) compared to 13 controls (1.6%; OR 0.27, 95% CI 0.03-2.1; p = 0.33). SPINK1 N34S was enriched in the TCP population 67/174 (38.5%) compared to controls 10/234 (4.3%; OR 14, 95% CI 6.9-28.3; p < 0.001).

CONCLUSION

G191R PRSS2 is a rare allele in the Indian population and the data suggest a nonsignificant trend towards a protective effect. N34S SPINK1 represents the major genetic risk factor in TCP.

摘要

背景/目的：热带钙化性胰腺炎（TCP）是一种在亚洲流行的特发性胰腺炎。胰蛋白酶抑制剂（SPINK1）N34S变异部分解释了TCP的遗传易感性。由于阴离子胰蛋白酶原（PRSS2）G191R可预防欧洲人的慢性胰腺炎，我们研究了该变异是否能预防印度人的TCP。

方法

我们从两家印度三级医疗转诊医院招募了174例患者和794名对照。我们通过熔解曲线分析、等位基因特异性鉴别分析和测序分析PRSS2和SPINK1变异。

结果

在1例TCP患者（0.6%）中检测到G191R，而在13名对照中（1.6%；OR 0.27，95%CI 0.03 - 2.1；p = 0.33）。与对照10/234（4.3%；OR 14，95%CI 6.9 - 28.3；p < 0.001）相比，SPINK1 N34S在TCP人群中更为富集，为67/174（38.5%）。