Single Nucleotide Polymorphisms in the Vitamin D Receptor Gene (VDR) May Have an Impact on Acute Pancreatitis (AP) Development: A Prospective Study in Populations of AP Patients and Alcohol-Abuse Controls

Abstract

Vitamin D imbalance is suggested to be associated with the development of pancreatitis. Single nucleotide polymorphisms (SNPs), Apa-1, Bsm-1, Fok-1, and Taq-1, in the vitamin D receptor gene (VDR) are known in various diseases, but not yet in pancreatitis. The aim of this study was to explore possible associations of the four SNPs in the VDR receptor gene in a population of acute pancreatitis patients and alcohol-abuse controls, and to investigate the association with acute pancreatitis (AP) susceptibility. The study population (n = 239) included acute pancreatitis patients (n = 129) and an alcohol-abuse control group (n = 110). All patients met the Diagnostic and Statistical Manual of Mental Disorders (DSM IV) criteria for alcohol dependence. DNA was extracted from peripheral leukocytes and analyzed for VDR polymorphisms using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Odd ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression analysis. To date, we have found allele T in Taq-1 (OR = 2.61; 95% CI: 1.68–4.03; p < 0.0001) to be almost three times more frequent in the AP group compared to the alcohol-abuse control patients. Polymorphism Taq-1 occurring in the vitamin D receptor may have an impact on the development of acute pancreatitis due to the lack of the protective role of vitamin D.

Impact of the etiology and Vitamin D receptor TaqI rs731236 gene polymorphism on the severity of acute pancreatitis

“…Also, the presence of the TT genotype was four times more frequent in the AP group (OR = 4.55; 95% CI: 1.69-12.20; P = .003) in comparison to the control group. 26 VDR signaling may be reduced or even activated dependent on the occurrence of specific single nucleotide polymorphism in AP similar to what has been described in the progression of some tumors. Vitamin D reduces oxidative stress through the induction of antioxidant activity by itself, and, importantly, oxidative damage has been implicated in acute pancreatitis initiation.…”

Tanshinone IIA Protects against Acute Pancreatitis in Mice by Inhibiting Oxidative Stress via the Nrf2/ROS Pathway

“…Our previous study indicated that oxidative stress and Nrf2/HO-1 pathway were dynamically changed in pancreatic tissue of AP mice and were the most significant at the peak of inflammatory response [16]. Many clinical studies and animal experiments also showed the role of oxidative stress and ROS generation in the pathophysiological response of AP, activation of Nrf2/HO-1 pathway, and reduction of ROS generation, which showed the protective effect against AP [33][34][35][36]. Additionally, after reanalyzing the sequencing results of relevant research [37], we found that HO-1 increased significantly in the AP mouse model induced by caerulein (3.38-fold change vs. normal, p = 0:0001), while other related genes including Keap1, NQO1, and GCLM had no significant changes.…”

Vitamin D and Human Health

“…Furthermore, the effects of the VDR SNPs were also investigated in acute pancreatitis (AP). It was found that a particular SNP (allele T in Taq 1) is almost three times more frequent in AP patents in comparison with alcohol-abuse controls [7]. Thus, it seems that alteration in vitamin D signaling through the presence of unique SNPs in the VDR gene may be associated with predisposition to certain pathologies.…”