BACKGROUND/AIMS: Irritable bowel syndrome (IBS) is a multifaceted disorder that afflicts millions of individuals worldwide. IBS is currently diagnosed based on the presence/duration of symptoms and systematic exclusion of other conditions. A more direct manner to identify IBS is needed to reduce healthcare costs and the time required for accurate diagnosis. The overarching objective of this work is to identify gene expression-based biological signatures and biomarkers of IBS. METHODS: Gene transcripts from 24 tissue biopsy samples were hybridized to microarrays for gene expression profiling. A combination of multiple statistical analyses was utilized to narrow the raw microarray data to the top 200 differentially expressed genes between IBS versus control subjects. In addition, quantitative polymerase chain reaction was employed for validation of the DNA microarray data. Gene ontology/pathway enrichment analysis was performed to investigate gene expression patterns in biochemical pathways. Finally, since vitamin D has been shown to modulate serotonin production in some models, the relationship between serum vitamin D and IBS was investigated via 25-hydroxyvitamin D (25[OH]D) chemiluminescence immunoassay. RESULTS: A total of 858 genetic features were identified with differential expression levels between IBS and asymptomatic populations. Gene ontology enrichment analysis revealed the serotonergic pathway as most prevalent among the differentially expressed genes. Further analysis via real-time polymerase chain reaction suggested that IBS patient-derived RNA exhibited lower levels of tryptophan hydroxylase-1 expression, the enzyme that catalyzes the rate-limiting step in serotonin biosynthesis. Finally, mean values for 25(OH)D were lower in IBS patients relative to non-IBS controls. CONCLUSIONS: Values for serum 25(OH)D concentrations exhibited a trend towards lower vitamin D levels within the IBS cohort. In addition, the expression of select IBS genetic biomarkers, including tryptophan hydroxylase 1, was modulated by vitamin D. Strikingly, the direction of gene regulation elicited by vitamin D in colonic cells is “opposite” to the gene expression profile observed in IBS patients, suggesting that vitamin D may help “reverse” the pathological direction of biomarker gene expression in IBS. Thus, our results intimate that IBS pathogenesis and pathophysiology may involve dysregulated serotonin production and/or vitamin D insufficiency.
Biomarkers ; Biopsy ; Cohort Studies ; Colon ; Diagnosis ; Gene Expression Profiling ; Gene Expression ; Gene Ontology ; Health Care Costs ; Humans ; Immunoassay ; Irritable Bowel Syndrome ; Luminescence ; Oligonucleotide Array Sequence Analysis ; Polymerase Chain Reaction ; Real-Time Polymerase Chain Reaction ; RNA ; Serotonin ; Transcriptome ; Tryptophan ; Tryptophan Hydroxylase ; Vitamin D ; Vitamins

OBJECTIVETo assess the impact of metabolic syndrome(MS) on Framingham risk score(FRS) in patients with type 2 diabetes mellitus (T2DM).

METHODSThe anthropometric and biochemical data of 1708 patients with T2DM admitted in hospital from May 2008 to April 2013 were retrospectively analyzed, including 902 males and 806 females with a mean age of 57.1±11.8 years (20-79 years). Diagnosis of MS was made according to the criteria of the Adult Treatment Panel Ⅲ Criteria modified for Asians.

RESULTSCompared to non-MS/T2DM patients, MS/T2DM patients had higher waist circumference, body weight, body mass index, systolic and diastolic blood pressure, fasting C peptide, total cholesterol, triglyceride, and LDL-C (P<0.05), while lower HDL-C (P<0.01). Both FRS [13.0(10.0, 15.0) vs 11.0(9.0, 13.0) in male,15.0(12.0, 18.0) vs 12.0(6.0, 14.8) in female,P<0.01)] and 10-year cardiovascular risk [12.0%(6.0%, 20.0%) vs 8.0%(5.0%,12.0%) in male,3.0%(1.0%, 6.0%) vs 1.0%(0.0%, 2.8%) in female,P<0.01] were higher in MS/T2DM patients than those in non-MS/T2DM patients.Both FRS and 10-year cardiovascular risk were increased with the components of MS.

CONCLUSIONT2DM patients with MS have more cardiovascular risk factors, higher FRS and 10-year cardiovascular risk.