ApaI Polymorphism in the Vitamin D Receptor Gene Decreases the Risk of Perianal Fistulas in Crohn’s Disease

• Published in: Nutrients Vol. 16; no. 20; p. 3485
• Main Authors: Gisbert-Ferrándiz, Laura, Llau, Jorge, Ortiz-Masia, Dolores, Cosín-Roger, Jesús, Macias-Ceja, Dulce Carolina, Hinojosa, Joaquín, Calatayud, Sara, Barrachina, Maria Dolores
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 14.10.2024; MDPI
• Subjects: Adult; Alfacalcidol; Anorectal fistula; Calcifediol; Complications and side effects; Crohn Disease - genetics; Crohn's disease; Ethnicity; Female; Fibroblasts; Fibroblasts - metabolism; Fistula; Genetic aspects; Genetic Predisposition to Disease; Genotype; Genotype & phenotype; Haplotypes; Health aspects; Hospitals; Humans; Inflammatory bowel disease; Linkage Disequilibrium; Male; Middle Aged; Physiological aspects; Polymorphism; Polymorphism, Single Nucleotide; Receptors, Calcitriol - genetics; Rectal Fistula - genetics; Risk Factors; Single nucleotide polymorphisms; Surgery; Vitamin D; White people; Young Adult; Spain; United States > US; Germany; BsmI; TaqI; fibroblasts; FokI; penetrating behavior; ApaI; perianal fistula; vitamin D receptor; single-nucleotide polymorphisms; Crohn’s disease
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu16203485

Background: Vitamin D, through the activation of its receptor (VDR), plays an immunomodulatory role in the gastrointestinal tract. Single-nucleotide polymorphisms (SNPs) in the VDR gene have been associated with Crohn’s disease (CD) risk, and patients carrying the TaqI polymorphism in this gene run a higher risk of developing a penetrating behavior. Aims: We analyzed the association of BsmI, ApaI, TaqI, and FokI SNPs in the VDR gene with the clinical characteristics of CD. Methods: Four polymorphisms identified in the VDR gene (BsmI, FokI, ApaI, and TaqI) were genotyped in blood samples from CD patients (n = 115) by using PCR-RFLP. The disease’s location and behavior and the presence of perianal fistulas were collected from each patient. Intestinal fibroblasts from ileal resections of CD patients (n = 10) were genotyped, and the expression of fibrotic and inflammatory markers was analyzed by RT-PCR. Results: The data reveal no association between any of the polymorphisms and CD risk. A strong linkage disequilibrium was detected between TaqI and both ApaI and BsmI, which in turn were strongly associated. Homozygosis or heterozygosis for the a allele of the ApaI SNP or b allele of the BsmI SNP was significantly associated with a lower risk of a penetrating behavior, while the aa genotype was associated with a lower risk of perianal fistulas. Fibroblasts carrying the aa genotype expressed lower levels of fibrotic and inflammatory markers. Conclusion: The aa genotype of the ApaI SNP in the VDR gene is associated with a lower risk of perianal fistulas in CD and a reduced expression of fibrotic and inflammatory markers in intestinal fibroblasts.