Exploring celiac disease candidate pathways by global gene expression profiling and gene network cluster analysis.

Celiac disease (CeD) is a gastrointestinal autoimmune disorder, whose specific molecular basis is not yet fully interpreted. Therefore, in this study, we compared the global gene expression profile of duodenum tissues from CeD patients, both at the time of disease diagnosis and after two years of the gluten-free diet. A series of advanced systems biology approaches like differential gene expression, protein-protein interactions, gene network-cluster analysis were deployed to annotate the candidate pathways relevant to CeD pathogenesis. The duodenum tissues from CeD patients revealed the differential expression of 106 up- and 193 down-regulated genes. The pathway enrichment of differentially expressed genes (DEGs) highlights the involvement of biological pathways related to loss of cell division regulation (cell cycle, p53 signalling pathway), immune system processes (NOD-like receptor signalling pathway, Th1, and Th2 cell differentiation, IL-17 signalling pathway) and impaired metabolism and absorption (mineral and vitamin absorptions and drug metabolism) in celiac disease. The molecular dysfunctions of these 3 biological events tend to increase the number of intraepithelial lymphocytes (IELs) and villous atrophy of the duodenal mucosa promoting the development of CeD. For the first time, this study highlights the involvement of aberrant cell division, immune system, absorption, and metabolism pathways in CeD pathophysiology and presents potential novel therapeutic opportunities.

Association of Four Missense SNPs with Preeclampsia in Saudi Women.

OBJECTIVE: The objective of this study was to investigate the association of rs1051740, rs2234922 (in microsomal epoxide hydrolase 1; EPHX1), rs268 (in lipoprotein lipase; LPL) and rs6025 (in Factor V Leiden; F5) genetic variants with the risk of preeclampsia development in Saudi women. MATERIALS AND METHODS: This case-control study recruited 233 Saudi women (94 preeclampsia cases and 139 healthy controls) who visited the Gynecology and Obstetrics Departments of two hospitals in Jeddah, Saudi Arabia, for routine postpregnancy clinical follow-ups. All the women underwent thorough clinical and biochemical investigations conducted according to the standard clinical guidelines. Genotyping of the study participants was done using real-time polymerase chain reaction-based TaqMan allelic discrimination assay. The strength of the association between genetic variants and disease development was assessed using chi-square, odds ratio, 95% confidence interval and multifactor dimensionality reduction tests. RESULT: The minor alleles "G" in rs268 (LPL) and "A" in rs6025 (F5) were absent in Saudi women. The frequencies of rs1051740 and rs2234922 of EPHX1, both in the homozygous and allelic forms, were not significantly different between preeclampsia patients and healthy controls (for all tests, P > 0.05). The multifactor dimensionality reduction analysis also indicated that the interaction between the four studied single-nucleotide polymorphisms (SNPs) had no significant association with preeclampsia risk. CONCLUSION: This study found that none of the studied genetic variants (neither the single SNP nor the SNP-SNP interactions) explain the development of preeclampsia in the Saudi population. These findings not only underscore the disease heterogeneity but also highlight the need to develop population-specific diagnostic genetic biomarkers for preeclampsia.