Scale and Scope of Gene-Alcohol Interactions in Chronic Pancreatitis: A Systematic Review

Genes

Jian-Min Chen¹  Claude Férec¹  Emmanuelle Génin¹  AnthonyF. Herzig¹  DavidN. Cooper²  Emmanuelle Masson³ 

[1] EFS, Univ Brest, Inserm, UMR 1078, GGB, F-29200 Brest, France;Institute of Medical Genetics, School of Medicine, Cardiff University, Cardiff CF10 3XQ, UK;Service de Génétique Médicale et de Biologie de la Reproduction, CHRU Brest, F-29200 Brest, France;

关键词: genetic predisposition to disease;    gene dosage effect;    genetic variation;    genome-wide association study;    human;   

DOI  :  10.3390/genes12040471

来源: DOAJ

【 摘 要 】

Background: Excessive alcohol consumption has long been known to be the primary cause of chronic pancreatitis (CP) but genetic risk factors have been increasingly identified over the past 25 years. The scale and scope of gene-alcohol interactions in CP nevertheless remain unclear. Methods: All studies that had obtained genetic variant data concurrently on alcoholic CP (ACP) patients, non-ACP (NACP) patients and normal controls were collated. Employing normal controls as a common baseline, paired OR_ACP and OR_NACP (odds ratios associated with ACP and NACP, respectively) values were calculated and used to assess gene-alcohol interactions. Results: Thirteen variants involving PRSS1, SPINK1, CTRC, CLDN2, CPA1, CEL and CTRB1-CTRB2, and varying from very rare to common, were collated. Seven variants had an OR_ACP > OR_NACP, which was regarded as an immediate indicator of gene-alcohol interactions in CP. Variants with an OR_ACP < OR_NACP were also found to interact with alcohol consumption by virtue of their impact on age at first pancreatitis symptoms in ACP. Conclusions: This study revealed evidence for extensive gene-alcohol interactions in CP. Our findings lend support to the hypothesis that alcohol affects the expression of genetically determined CP and highlight a predominant role of weak-effect variants in the development of ACP.

【 授权许可】

Unknown