BST1 rs11724635 interacts with environmental factors to increase the risk of Parkinson's disease in a Taiwanese population
PARKINSONISM & RELATED DISORDERS
Authors: Chen, Meng-Ling; Lin, Chin-Hsien; Lee, Ming-Jen; Wu, Ruey-Meei
Abstract
A recently published genome-wide association study in Caucasian and Asian populations showed a significant association between the bone marrow stromal cell antigen 1 (BSTI) SNP rs11724635 and increased risk for Parkinson's disease (PD). To investigate whether BSTI rs11724635 increases the risk of PD, either by itself or in combination with environmental factors, we performed an association analysis of BSTI rs11724635 in a large cohort of Taiwanese patients with PD and age matched controls. The study used TaqMan genotyping, logistic regression, and haplotype methods. The genotype distribution of rs11724635 in PD patients (N = 468; p = 0.50) and control subjects (N = 487; p = 0.44) was consistent with Hardy-Weinberg equilibrium. Compared with the AA genotype, the frequency of both CA and CC genotypes was not significantly different between the patient and control groups. The adjusted odd ratios (ORs) for CA and CC were not statistically significant (CA: OR = 0.962, 95% CI = 0.643-1.439, p = 0.850; CC: OR = 0.992, 95% CI = 0.654-1.503, p = 0.969). Of note, ever use of well water before the onset of PD symptoms had an impact on the occurrence of PD through interactions with BST1 rs11724635 AC (OR = 1.453, p = 0.024) and CC (OR = 1.623, p = 0.008). Our results show that the BST1 rs11724635 polymorphism alone is not associated with the development of PD, but it can interact with well water drinking to increase the risk of PD in this Taiwanese population. (C) 2013 Elsevier Ltd. All rights reserved.
The mTORC1 signaling modulated by intracellular C3 activation in Paneth cells promotes intestinal epithelial regeneration during acute injury
INTERNATIONAL IMMUNOPHARMACOLOGY
Authors: Ye, Jinning; Yuan, Kaitao; Dai, Weigang; Sun, Kaiyu; Li, Guanghua; Tan, Min; Song, Wu; Yuan, Yujie
Abstract
Complement activation is associated with regional inflammation during acute gastrointestinal injury (AGI). This study is designed to explore how intracellular C3 activation in Paneth cells (PCs) affects regeneration of intestinal epithelium during AGI. AGI was induced in wildtype C57BL/6 mice, with sham operation employed as control. Exogenous C3 (1 mg, I.P.) was applied at 6 h post-surgery. Intestinal crypts harvested from ileum were cultured with presence or absence of C3 (20 g/ml), with small interfering RNA against BSTI and complement activation inhibitor selectively applied in vitro. The intestinal integrity, percentage of PCs and intestinal stem cells (ISCs) were evaluated. Importantly, cADPR, C3 fragments, and S6-related proteins were detected in PCs to inspect the mammalian target of rapamycin complex 1 (mTORC1) signaling. AGI caused breakdown of intestinal mucosa integrity and regional inflammation. Exogenous C3 by itself failed to promote the growth of intestinal epithelium, but distinctly enhanced the activity of PCs via intracellular activation, which subsequently supported the expansion of ISCs inside of intestinal crypts. Inhibition of C3 activation was associated with decreased expressions of S6, S6K1 and cADPR, with blocking BST1 found to depress cADPR only. Collectively, these data confirmed intracellular activation of C3 in PCs enhanced expansion of ISCs in response to acute injury. The mTORC1 signaling pathway in PCs contributed to this crosstalk during exogenous C3 treatment.