Visceral adiposity, genetic susceptibility, and risk of complications among individuals with crohn's disease

Introduction: Adipose tissue in mesenteric fat plays a key role in systemic and luminal inflammation through production of Tumor Necrosis Factor-α (TNF-α) and inhibition of adiponectin, an anti-inflammatory cytokine, in patients with Crohn's disease (CD). However, little is known about the role of visceral adipose tissue (VAT) and its interaction with genetic predisposition on CD progression. We therefore sought to examine the association between VAT and its interaction with genetic susceptibility on risk of CD complications. Methods: We conducted a cross-sectional study of CD patients enrolled in Prospective Registry in Inflammatory Bowel Disease Study at Massachusetts General Hospital (PRISM). Information on diagnosis of CD and its complications were collected and confirmed through review of medical records. VAT volume was measured from CT scans prior to development of disease complications, using Aquarius 3D (TeraRecon Inc., version 4.4.12). A genetic risk score was calculated using previously reported single nucleotide polymorphisms (SNPs) associated genome-wide with CD susceptibility. We used logistic regression models to estimate the multivariable-adjusted odds ratio (MV-adjusted OR) and 95% confidence interval (CI) while adjusting for age at diagnosis, duration of disease, body mass index (BMI), and smoking. We evaluated for effect modification by genetic predisposition using multiplicative interaction terms. Results: Among 470 CD patients with available data on VAT, 73 required surgery, 57 with penetrating disease, 60 with stricturing disease, and 143 with perianal disease. The risk of surgery appeared to increase with higher VAT volume (Ptrend = 0.007). Specifically, compared to individuals in the lowest quartile of VAT volume (≤ 904 cm3), the MV-adjusted OR of surgery among individuals in the highest quartile (> 3809 cm3) was 5.75 (95% CI, 1.61-20.56). We did not observe an association between VAT volume and risk of penetrating, structuring, or perianal disease (All Ptrend > 0.40). We also explored the possibility that the effect of VAT on CD complications may be modified by genetic predisposition as assessed by genetic risk score and observed no effect modification (All Pinteraction > 0.25). Conclusions: In this cohort of patients with CD, we show that VAT volume measured prior to development of disease complications may be associated with a significantly increase in risk of surgery. Taken together with previous findings that BMI is not associated with risk of CD complications, our data suggest that visceral adiposity as measured by VAT and not total obesity, may negatively impact long-term progression of CD. (Figure Presented).