Background Vitamin D (VD) is a fat-soluble vitamin essential for calcium homeostasis and that acts at the extraskeletal level. UVB skin exposure allows the synthesis of provitamin D. This undergoes a first hydroxylation in the leaver by the CYP2R1 enzyme and a second hydroxylation in the kidney by the CYP27B1 enzyme: active VD is obtained. VD is transported into the circulation by VDBP and exerts its activity in the target cells binding its VDR receptor. Finally, VD is inactivated by the renal enzyme CYP24A1. Perianal disease (pCD) is a severe phenotypic manifestation of CD that may present as perianal fistula, abscess, recto-vaginal fistula, or stenosis. Among the mechanisms involved in its pathogenesis we recognise local inflammation and intestinal microbiota alteration. Vitamin D (VD) seems to act on these elements. As there are currently no studies on this subject in the literature, the aim of this study is to evaluate the presence of an association between SNPs of genes coding for enzymes, transporters and receptors involved in the VD pathway and the occurrence of pCD in CD patients. Methods The study was carried out on the biological samples of 206 patients with CD, including 34 with pCD, who were followed up at the inflammatory bowel disease clinic in Turin, Italy. Through the use of Real-Time PCR, the genotype distribution of the following genes were assessed: VDR, CYP27B1, CYP24A1, and GC. For the association study, chi-square test was performed with calculation of p value and, when significant, logistic regression and calculation of OR with 95% CI was performed. Results Studying the association between SNPs and the presence of pCD, the following results were obtained: BsmI p=0.0470 and Apal p=0.0251. For BsmI heterozygous genotype there was an OR=2.5 (95% CI 1.2-5.3) of developing perianal disease and p value=0.02, while for ApaI heterozygous there was OR=2.91 (95% CI 1.3-6.6) of presenting pCD, with p value=0.01. Conclusion In the literature, there are several studies examining the association between the heterozygous Aa genotypes of ApaI and Bb genotypes of BsmI and increased inflammatory markers. In addition, some studies suggest that these two genotypes represent a risk factor for some diseases, including multiple myeloma, systemic lupus erythematosus, and mild cognitive disorder. This study demonstrates for the first time an impact of polymorphisms of genes associated with the VD pathway in predicting the onset of pCD. Specifically, the presence of the heterozygous genotype of BsmI and ApaI significantly increases the risk. Future studies need to be performed in different and larger cohorts of patients in order to confirm these data.

中文翻译：

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P1200 维生素D代谢基因多态性与克罗恩病肛周疾病的相关性研究

背景维生素 D (VD) 是一种对钙稳态至关重要的脂溶性维生素，在骨骼外水平发挥作用。UVB 皮肤暴露可促进维生素原 D 的合成。维生素原 D 在叶子中通过 CYP2R1 酶进行第一次羟基化，并在肾脏中通过 CYP27B1 酶进行第二次羟基化：获得活性 VD。VD 通过 VDBP 转运到循环系统中，并在结合其 VDR 受体的靶细胞中发挥其活性。最后，VD 被肾酶 CYP24A1 灭活。肛周疾病 (pCD) 是 CD 的一种严重表型表现，可能表现为肛周瘘、脓肿、直肠阴道瘘或狭窄。在其发病机制中，我们认识到局部炎症和肠道微生物群的改变。维生素 D (VD) 似乎对这些元素起作用。由于目前文献中还没有关于这一主题的研究，本研究的目的是评估编码参与 VD 途径的酶、转运蛋白和受体的基因 SNP 与 CD 患者中 pCD 的发生之间是否存在关联。方法 对意大利都灵炎症性肠病诊所随访的 206 例 CD 患者（其中 34 例 pCD）的生物样本进行研究。通过使用实时 PCR，评估了以下基因的基因型分布：VDR、CYP27B1、CYP24A1 和 GC。对于关联研究，进行卡方检验并计算 p 值，当显着时，进行逻辑回归并计算 OR（95% CI）。结果 研究 SNP 与 pCD 存在之间的关联，获得以下结果：BsmI p=0.0470 和 Apal p=0.0251。对于 BsmI 杂合基因型，发生肛周疾病的 OR=2.5 (95% CI 1.2-5.3)，p 值=0.02，而对于 ApaI 杂合基因型，出现 pCD 的 OR=2.91 (95% CI 1.3-6.6)，其中p值=0.01。结论 在文献中，有几项研究探讨了 ApaI 的杂合 Aa 基因型和 BsmI 的 Bb 基因型与炎症标志物增加之间的关联。此外，一些研究表明，这两种基因型代表了一些疾病的危险因素，包括多发性骨髓瘤、系统性红斑狼疮和轻度认知障碍。这项研究首次证明了与 VD 通路相关的基因多态性对预测 pCD 发病的影响。具体来说，BsmI 和 ApaI 杂合基因型的存在显着增加了风险。未来的研究需要在不同的、更大的患者群体中进行，以证实这些数据。