Background: Zinc deficiency (ZD) in Crohn's disease (CD) is common, may exacerbate disease activity and is found even in patients with clinical remission. Previous literature indicates positive effects of zinc on intestinal repair and tight junction permeability as well as anti-inflammatory activity via zinc homeostasis and activation of autophagy. In view of the latter, ZD might increase the impact of the autophagy-related 16-like 1 (ATG16L1) single nucleotide polymorphism (SNP), a key player in autophagy, which is known to be associated with an increased risk of CD. We aimed to assess the prevalence of ZD in CD patients in clinical remission and to analyze both a potential impact on future disease course as well as an interplay with the presence of mutated ATG16L1.
Methods: Zinc levels from CD patients in clinical remission at baseline and an uncomplicated disease course within the next 3 years (n=47) were compared with those from patients developing complications (n=50) defined as either 1) flare up or 2) need for new anti-TNF or 3) development of stenosis, abscess, fistula or anal fissure. All data was available from the Swiss IBD cohort study.
Results: Mean zinc level in the 97 patients (mean age 40.4±15.7y, 44.3% males, median CDAI at baseline 34.0 [IQR 11.0–53.0]; no prior or current anti-TNF treatment) was 18.0±4.7umol/L. No absolute ZD (defined as <11umol/L) was observed. Low zinc levels (defined as <15.1umol/L) were found in 28 patients (28.9%). Males had significantly higher zinc levels compared to females (19.4±5.7 vs. 16.8±3.3, p=0.006) and proportion of patients with low zinc levels was higher among females (20/54, 37.0% vs. 8/43, 18.6%, p=0.047). Zinc levels of patients with a future complicated disease course were not different from those of patients without complications (17.7±4.3 vs. 18.3±5.1, n.s.). ATG16L1 SNP analysis was available for 61 patients (62.9%) with 25 (25/61, 41.0%) carrying the SNP rs2241880 (T300A). Zinc levels of patients with ATG16L1 (T300A) did not differ from those of patients without (16.3±2.7 vs. 17.1±3.2, n.s.). Looking only at ATG16L1 (T300A) carriers, no difference in zinc levels between patients with vs. without a complicated disease course was seen (16.0±2.6 vs. 17.3±2.9, n.s). In a multivariate regression model adjusted for age, sex, diagnostic delay, prior/current immunomodulation and presence of ATG16L1 (T300A), zinc levels at baseline did not predict complicated disease outcome (OR 0.80, 95% CI 0.60–1.06).
Conclusions: We did not observe ZD in CD patients in clinical remission. However, zinc levels among females were lower compared to those among males. Zinc levels at baseline did not predict complicated disease course, neither in CD patients overall nor ATG16L1 (T300A) carriers.