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P663. Association of HIF1α pathway genes with relevant clinical subphenotypes in inflammatory bowel disease (IBD)

P.M. Linares1, M.E. Fernández-Contreras1, M. Chaparro1, A. Juliá2, R. Tortosa2, S. Marsal2, J.P. Gisbert1, 1Hospital Universitario de La Princesa, IP and CIBERehd, Gastroenterology Unit, Madrid, Spain, 2Vall d'Hebron Hospital Research Institute, Rheumatology Research Group, Barcelona, Spain

Background

The hypoxia-inducible HIF1α-activated genes include VEGFA, which is an angiogenesis promoter. Both factors are highly polymorphic and important regulators of the angiogenic development and inflammation during IBD pathogenesis. The aim of our study is to evaluate the association of HIF1α 1772C/T and VEGFA 2578A/C and VEGFA 634G/C genotype polymorphisms with Crohn's disease (CD) and ulcerative colitis (UC).

Methods

Patients with CD and patients with UC were included. DNA samples from peripheral blood were extracted and genotyped for one HIF1α single nucleotide polymorphism (SNP) (1772C/T) and two VEGFA SNPs (2578A/C and 634G/C). The genotype data from all three polymorphisms was obtained using the Illumina bead array genotyping platform Quad610.

Results

One hundred and seventy-one patients with IBD (103 UC, 68 CD) were included. The mean age was 45±21 years, and 53% were male. The mean disease duration was 12±7 years. Genotype frequencies are shown in Table 1.

The results of the comparison between wild type homozygous versus carriers of variant alleles by Odds-ratio (OR) analysis are shown in Table 2.

The homozygous 1772TT variant genotype was associated with risk of suffering UC, compared with CD. The allelic frequencies of the studied genotypes and the rate of carriers of variant alleles for 2578CC and 634CC were similar between patients with CD and UC. 1772TT SNP was associated with low risk of ileal location (OR 0.65, 95% CI 0.58–0.73; p < 0.0001) and stricturing behaviour (OR 0.89, 95% CI 0.85–0.95; p < 0.0001) in patients with CD, and extraintestinal manifestations (OR 0.82, 95% CI 0.76–0.89; p < 0.0001) in patients with IBD. SNP 634CC was associated with low risk of stricturing behaviour (OR 0.891, 95% CI 0.840–0.944; p < 0.0001) in patients with CD. No association regarding patients with UC was found.

Table 1. Genotype frequencies
CD (%)UC (%)
1772CC7880
1772CT2216
1772TT4
2578AA2022
2578AC5246
2578CC2832
634GG4039
634GC4948
634CC1113
Table 2. OR analysis for allelic frequencies
SNPOR value95% CIp-value
1772C/T0.5930.523–0.672<0.05
2578A/C1.5020.541–4.169N.S.*
634G/C1.2180.544–2.727N.S.*
*N.S. Not Significant.

Conclusion

HIF1α 1772TT genotype is associated with presence of UC (compared with CD) and with lower risk of extraintestinal manifestation in IBD. HIF1α 1772TT and VEGFA 634CC polymorphisms are associated with disease location and behaviour in CD but not in UC.