Author name:
ابتسام بداي حسان الكناني
Supervisor name:
بتول علي شهاب | علي حسين ادحية
Abstract:
Inflammatory bowel disease (IBD) is a world healthcare problem that involves two major forms : Crohn’s disease (CD) and ulcerative colitis (UC). Immunogenetic predisposition is one of the risk factors for the disease, and cytokines are among these factors. Therefore, the association between 13 SNPs (single nucleotide polymorphisms) of cytokine and cytokine receptor genes (IL1A, IL1B, IL1R1, IL1RN, IL2, IL4, IL4R, IL6, IL10, IL12B, IFNG, TNF and TGFB1) and IBD was determined in samples of Iraqi Arab patients (34 CD and 66 UC). The patients were referred to the Gastrointestinal Tract Unit at Al - Kindy Teaching Hospital, Al - Yarmouk Teaching Hospital and Al - Zuafrania General Hospital in Baghdad for diagnosis and treatment during the period August 2013 - October 2014. A control sample of 43 individuals was also included.The following results were reached by the study : 1. Interleukin - 1 alpha gene (IL1A - 889) : frequencies of CC genotype and C allele were significantly increased in CD (58.8 and 73.5%, respectively) and UC (54.6 and 71.2%, respectively) patients compared to controls (25.5 and 40.7%, respectively). In contrast, TT genotype and T allele frequencies were significantly decreased in CD (11.8 and 26.5%, respectively) and UC (12.1 and 28.8%, respectively) patients compared to controls (44.2 and 59.3%, respectively).2. Interleukin - 1 beta gene (IL1B - 511) : Frequency of TC genotype was significantly increased in UC patients compared to controls (63.6 vs. 39.5%; P = 0.018), while CC genotype frequency was decreased (6.1 vs. 32.2%; P = 0.061). No variation was observed in CD patients.3. Interleukin 1 receptor type 1 gene (IL1R1pstl 1970) : Frequencies of TT genotype and T allele (47.1 and 67.7%, respectively) were significantly increased (P = 0.026 and 8.6*10 - 5, respectively) in CD patients compared to controls (20.9 and 34.97%, respectively). In contrast, CC genotype (11.8 vs. 51.2%) and allele C (32.4 vs. 65.1%) frequencies were significantly decreased (P = 2.8*10 - 4 and 8.6*10 - 5, respectively) in CD patients. For UC, the patients demonstratedgnificant increased frequencies of TC genotype (48.5 vs. 27.9%; P = 0.045) and T allele (63.6 vs. 34.9%; P = 5.1*10 - 5) compared to controls. As in CD, UC patients also demonstrated significant decreased frequencies of CC genotype (12.1 vs. 51.2%; P = 1.7*10 - 5) and C allele (36.4 vs. 65.1%; P = 8.6*10 - 5).4. Interleukin 2 gene (IL2+166) : Among CD patients, frequencies of TT genotype (41.2 vs. 6.9%) and T allele (64.7 vs. 43.0%) were significantly increased in patients compared to controls (P = 0.001 and 0.009, respectively). In contrast, TG genotype (47.1 vs. 72.1%; P = 0.035) and G allele (35.3 vs. 56.9%; P = 0.009) frequencies were significantly decreased. Almost, similar observations were made in UC patients.5. Interleukin 4 gene (IL4 - 590) : it was observed that frequencies of TT genotype (52.9 vs. 11.6%; P = 1.2*10 - 4) and T allele (70.6 vs. 24.4%; P = 1.6*10 - 8) were significantly increased in CD patients compared to controls. In contrast, CC genotype (11.8 vs. 62.8%, P = 5.6*10 - 6) and C allele (29.4 vs. 75.6%; P = 1.6*10 - 8) frequencies were significantly decreased. In the case of UC, frequencies of TC genotype (69.7 vs. 25.6%; P = 1.1*10 - 5) and T allele (62.1 vs. 24.4%; P = 4.6*10 - 8) were significantly increased in patients, while CC genotype (3.0 vs. 62.8%; P = 2.5*10 - 12) and C allele (37.9 vs. 75.6%; P = 1.6*10 - 8) frequencies were significantly decreased in patients.6. Interleukin 4 receptor gene (IL4R+1902) : frequencies of GG genotype (47.1 vs.11.6%) and G allele (55.9 vs. 37.2%) were significantly increased in CD patients compared to controls (P = 0.001 and 0.023, respectively). In contrast, GA genotype (17.7 vs. 51.1%; P = 0.004) and A allele (44.1 vs. 62.8%; P = 0.023) frequencies were significantly decreased. In UC patients, frequencies of GG genotype (57.6 vs. 11.6%) and G allele (75.8 vs. 37.2%) were significantly increased (P = 1.0*10 - 6 and 1.9*10 - 8, respectively); while frequencies of AA genotype (6.1 vs. 37.2%; P = 7.0*10 - 5) and A allele (24.2 vs. 62.8%; P = 1.9*10 - 8) were significantly decreased.7. Interleukin 6 gene (IL6+565) : Comparing patients to controls revealed that GG genotype frequency was significantly increased in CD (70.6 vs. 13.9%; P = 1.5*10 - 8) and UC (69.7 vs. 13.9%; P = 4.4*10 - 7) patients, and a similar increased frequency of G allele was observed. In contrast, the GC genotype frequency was significantly decreased in CD (23.5 vs. 76.7%; P = 3.7*10 - 6) and UC (24.2 vs. 76.7%; P = 7.0*10 - 6) patients.8. Interleukin 12B gene (IL12B - 1188) : Frequency of A allele was significantly increased in CD patients compared to controls (67.7 vs. 47.7%; P = 0.015), while C allele was significantly decreased (32.4 vs. 52.3%; P = 0.015). For UC, the heterozygous genotype AC showed a significant increased frequency in patients compared to controls (66.7 vs. 30.2%; P = 3.6*10 - 4), while CC genotype frequency was significantly decreased (6.1 vs. 37.2%; P = 7.0*10 - 5). 9. Interferon gamma gene (IFNG+874) : The AT genotype showed a significant increased frequency in CD patients compared to controls (58.8 vs. 30.2; P = 0.020), while TT genotype frequency was significantly decreased (11.8 vs.39.5%; P = 0.009). For UC, AA genotype (54.6 vs. 30.2%; P = 0.018) and A allele (74.2 vs. 45.4; P = 2.7*10 - 5) frequencies were significantly increased in patients. In contrast, TT genotype (6.1 vs. 39.5%; P = 2.8*10 - 5) and T allele (25.8 vs. 54.7%; P = 2.7*10 - 5) frequencies were significantly decreased. 10. Tumor necrosis factor alpha gene (TNF - 308) : Comparing CD patients to controls revealed no significant variation, while UC patients demonstrated a significantly (P = 0.006) increased frequency of G allele (71.2 vs. 52.3%) and a decreased frequency of A allele (28.8 vs. 47.7%). 11. Interleukin 1 receptor antagonist (IL1RNmaspl 11100), interleukin 10 gene (IL10 - 1082) and Transforming growth factor beta (TGFB1codon 25) genes : Comparing patients to controls revealed no significant variations in genotype or allele frequencies.The presented results of the 13 cytokine SNPs in CD and UC patients are the first report in Iraqi patients, and their findings highlighted the role of these SNPs in etiopathogenesis of both groups of IBD, and paved the way for further investigations to determine the role cytokine gene polymorphisms in susceptibility to IBD or their protective effects.
