Role of polymorphisms in pathophysiology of Crohn's disease.

Aim: To establish the relationship of () polymorphisms and mycobacterial infections in Crohn's disease (CD).

Methods: All 133 subjects' blood samples were genotyped for nine single nucleotide polymorphisms (SNPs) in using TaqMan™ genotyping, while the effect of the SNPs on and γ gene expression was determined using RT-PCR. Detection of subspecies (MAP) gene was done by nPCR after DNA extraction from the isolated leukocytes of each subjects' blood samples. T-cells isolated from the patient samples were tested for response to phytohematoagglutonin (PHA) mitogen or mycobacterial antigens by BrdU proliferation assays for T-cell activity.

Results: Out of the nine SNPs examined, subjects with either heterozygous (TC)/minor (CC) alleles in occurred in 83% of CD subjects compared to 61% healthy controls (-values < 0.05; OR = 3.03). Subjects with either heterozygous (GA)/minor (AA) alleles in occurred in 16% of CD compared to 6% healthy controls (OR = 2.7). Gene expression in in CD subjects was significantly decreased by 2 folds compared to healthy controls (-values < 0.05). expression levels were found to be significantly increased by approxiately 2 folds in subjects when either heterozygous or minor alleles in and/or were found (-values < 0.05). MAP DNA was detected in 61% of CD compared to only 8% of healthy controls (-values < 0.05, OR = 17.52), where subjects with either heterozygous or minor alleles in and/or had more presence than subjects without SNPs did. The average T-cell proliferation in CD treated with PHA or mycobacteria antigens was, respectively, 1.3 folds and 1.5 folds higher than healthy controls without any significant SNP.

Conclusion: The data suggests that SNPs in affect the negative regulation of the immune response in CD patients, thus leading to an increase in inflammation/apoptosis and susceptibility of mycobacteria.