Objectives We sought association of genetic variants in the renin angiotensin system (RAS) and Vitamin D system with acute pancreatitis (AP) development and severity. Summary Background Data The endocrine RAS is involved in circulatory homeostasis through the pressor action of angiotensin II (ang II) at its AT1 receptor (AT1R). However, local RAS regulate growth and inflammation in diverse cells and tissues, and their activity may be suppressed by Vitamin D. Intra-pancreatic ang II generation has been implicated in the development of AP. Methods Five hundred and forty-four Caucasian AP patients from three countries (UK 22; Germany 136; Netherlands 386) and 8487 control subjects (UK 7833, Netherlands 717) were genotyped for eight polymorphisms of the RAS/vitamin D systems, chosen based on likely functionality. Results The ACE I (rather than D) allele was significantly associated with alcohol-related AP when all cohorts were combined (p=0.03). The Renin rs5707 G (rather than A) allele was associated with AP (p=0.002), infected necrosis (p=0.025) and mortality (p=0.046). Conclusions The association of two RAS polymorphisms with AP suggests the need for further detailed analysis of the role of RAS/Vitamin D in the genesis or severity of AP, particularly given the ready potential for pharmacological manipulation of this system using existing marketed agents. However, further replication studies will be required before any such association is considered robust, particularly given the significant heterogeneity of AP causation and clinical course.
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