METHODS: Data were obtained retrospectively from a review of the medical records of in- and out-patients with a diagnosis of UC at the University Hospital, Kuala Lumpur between 1985 and 1998.
RESULTS: There were 45 confirmed cases of UC of which 3 were foreigners, who were excluded from analysis. Thirty new cases of UC were diagnosed during the study period. Their mean age at presentation was 33.0+/-10.0 years. The highest prevalence of UC was 17.9/100 000 hospital admissions in the Indians, followed by 11.2/100 000 hospital admissions in the Chinese. The lowest prevalence was 3.7/100 000 hospital admissions in the Malays. The prevalence of UC was significantly higher in the Indians and the Chinese when compared with the Malays with an OR of 4.89 (CI = 2.02-12.24; chi2 = 15.45, P<0.001) and 3.06 (CI = 1.24-7.78; chi2 = 6.30; P = 0.012) respectively. The extent of colonic disease was similar in the Malay and Indian patients. In contrast, distal or left-sided colitis predominated in the Chinese with an OR of 8.17 (95%CI = 1.31-64.87; chi2 = 5.53, P = 0.02). Extraintestinal manifestations were uncommon (11.9%).
CONCLUSION: UC is an uncommon disease in Malaysia, but racial differences exist. The Indians had the highest prevalence of UC with the Chinese demonstrating the least extensive disease.
METHODS: We conducted transcriptome profiling on 32 colonic biopsies [11 long-duration UC, ≥20 years; and 21 short-duration UC, ≤5 years] using Affymetrix Human Transcriptome Array 2.0. Differentially expressed genes [fold change > 1.5, p < 0.05] and alternative splicing events [splicing index > 1.5, p < 0.05] were determined using the Transcriptome Analysis Console. KOBAS 3.0 and DAVID 6.8 were used for KEGG and GO analysis. Selected genes from microarray analysis were validated using qPCR.
RESULTS: There were 640 differentially expressed genes between both groups. The top ten upregulated genes were HMGCS2, UGT2A3 isoforms, B4GALNT2, MEP1B, GUCA2B, ADH1C, OTOP2, SLC9A3, and LYPD8; the top ten downregulated genes were PI3, DUOX2, VNN1, SLC6A14, GREM1, MMP1, CXCL1, TNIP3, TFF1, and LCN2. Among the 123 altered KEGG pathways, the most significant were metabolic pathways; fatty acid degradation; valine, leucine, and isoleucine degradation; the peroxisome proliferator-activated receptor signalling pathway; and bile secretion, which were previously linked with CAC. Analysis showed that 3560 genes exhibited differential alternative splicing between long- and short-duration UC. Among them, 374 were differentially expressed, underscoring the intrinsic relationship between altered gene expression and alternative splicing.
CONCLUSIONS: Long-duration UC patients have altered gene expressions, pathways, and alternative splicing events as compared with short-duration UC patients, and these could be further validated to improve our understanding of the pathogenesis of CAC.