RESUMO
Background: Both genetic and environmental factors play major roles in the development of inflammatory bowel disease [IBD]. Recent studies have identified a number of genetic susceptibility loci for Crohn's disease [CD] and ulcerative colitis [UC]
Objectives: The present study aimed at examining the association of nine polymorphisms in four different genes with the development of CD and UC in a sample of Saudi patients with IBD
Materials and Methods: All gene polymorphisms were identified by polymerase chain reaction and by direct sequencing. Allele and genotype frequencies of polymorphisms of NOD2/CARD15 [R702W, G908R, L1007finsC], Toll-like receptor 4 [TLR4] [D299G, T399I], OCTN promoter [C1672, G207C] and DLG5 [G113A, C4136A] genes were determined in Saudi subjects with CD [51], UC [26] and in 75 normal controls
Results: Out of the nine polymorphisms studied in four loci, only two polymorphisms in two different loci were found to have increased in patients compared with the control subjects. The CT genotype of TLR4 T3991 was over represented in patients with CD or UC compared to that in controls [odds ratios [OR], 5.63:95% confident interval [CI], 1.19-26.69; P = 0.03]. In addition, the GA genotype of DLG5 G113A was over represented in patients with CD or UC compared with that in controls [OR, 4.72:95% CI 2.30-9.66; P = 0.0001]. However, there were no significant associations found between all other polymorphisms studied and the susceptibility of CD or UC found in the Saudi population
Conclusion: Our finding indicates that association of IBD with nine gene polymorphisms was only significant in two of these polymorphic variants
RESUMO
Homozygosity for the C677T mutation in the gene of the thermolabile enzyme 5, 10 methylenetetrahydrofolate reductase [MTHFR] associates with reduced enzyme activity, leading to mild hyperhomocysteinemia. We now know that an elevated level of homocysteine is an important risk factor for cardiovascular disease [CVD]. The objective of this study was to determine the prevalence of the C677T mutation in Saudi patients diagnosed with CVD. Over a period of 2 years [2003-2004] in a case control study, we determined the prevalence of the C677T mutation in 83 CVD patients and in 40 age and gender-matched controls in the Eastern Province of Saudi Arabia. We determined the MTHFR genotype by restriction fragment length polymorphism and allele specific hybridization procedures. The CVD group showed over representation of the C677T allele frequencies [20.5%] compared with unaffected controls [15%] [p=0.3]. Furthermore, the genotypic data indicated that the prevalence of homozygosity for the C677T mutation was dramatically higher in the CVD patients [10.8%] when compared with normal [0%] [p=0.058]. These results suggest that the MTHFR C677T variant mildly influences CVD. However, we require further investigation in large independent samples