Clinical predictors of inflammatory bowel disease in a genetically well-defined Caucasian population.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC), the two main types of inflammatory bowel disease (IBD), are multifactorial conditions of unknown etiology. The objective of this study is to examine the combined gene-environment interactions influencing IBD susceptibility in a well-defined Caucasian cohort in rural mid-America. METHODS: Patients were diagnosed to have CD or UC using conventional radiologic, endoscopic, and/or histopathologic findings. Histological diagnosis was made by a single specialist gastrointestinal pathologist with a particular interest in IBD. Information regarding cigarette smoke exposure was obtained by administration of the Behavioral Risk Factor Surveillance System Survey (BRFSS) to all patients. Genomic DNA was extracted from peripheral blood leukocytes, and polymerase chain reaction (PCR) amplification and genotyping were performed for 11 Single Nucleotide Polymorphisms (SNP) in NOD2, IL23r, OCTN1 genes along with IGR. RESULTS: Our cohort consists of 1196 patients: 435 controls, 485 CD patients, and 276 UC patients. Only patients with genotype data for at least 7 of 11 SNPs were included in our data analysis. The control groups for all 11 SNPs were in Hardy-Weinberg Equilibrium. In genotype-association SNP analysis, all NOD2 SNPs (rs5743293, rs2066844, rs2066845) and the IL23r SNP (rs11465804) showed a significant association to IBD (p < 0.03). A multiple gene-interaction analysis showed an association between NOD2 and IL23r with UC (p = 0.04). There were no associations between any OCTN1 and IGR SNPs and IBD in this cohort. A multivariable logistic regression analysis showed that female gender, "current" or "former" smoking status, family history of IBD, and NOD2 SNP minor alleles were associated with CD. CONCLUSION: IBD remains to be challenging to properly diagnose, characterize, and treat. Our study proposes a combined genetic, phenotypic, and environmental approach in an attempt to better understand IBD. Previously demonstrated associations between OCTN1 and IGR and IBD were not confirmed.

Bilateral transverse sinus thrombosis secondary to a homozygous C677T MTHFR gene mutation.

We describe the case of a previously healthy young man who presented with headache, diplopia, nausea, vomiting, and bilateral papilledema. Magnetic resonance venography of the brain revealed thrombosis of the right transverse sinus. Blood tests showed elevated homocysteine levels, and coagulation studies revealed a homozygous C677T mutation and a heterozygous A1298C mutation of the methylenetetrahydrofolate reductase (MTHFR) gene. The patient had no other etiology for venous thrombosis. We recommend screening patients who present with sinus thrombosis for MTHFR gene mutations.

The prevalence of consanguineous marriages in an underserved area in Lebanon and its association with congenital anomalies.

BACKGROUND: Consanguinity is a recognized common practice among marriages in the Middle East. Many studies have suggested a strong association between first cousin marriages and the incidence of autosomal recessive diseases and congenital anomalies. The objectives of this study were to study the prevalence of consanguinity among the marriages of Bekaa (a region in Lebanon) with its sociodemographic correlates, and to assess the prevalence of congenital anomalies associated with these marriages. METHODS: This study was a cross-sectional study done in three of the major areas of the Bekaa region. The sample size consisted of 552 households chosen based on proportionate random sampling according to population size in each area. The survey was conducted based on face-to-face interview with a member of the couples of each household. RESULTS: The overall prevalence of consanguineous marriages was reported to be 42% with first cousin marriage constituting around 31% of the total marriages. No association was found between different socioeconomic status (SES) correlates and first cousin marriages. Results showed a significant association between first cousin marriage and mental retardation, physical retardation, bilateral cleft lip +/- cleft palate, cystic fibrosis, and congenital blindness. CONCLUSION: In a population with a high degree of inbreeding, the formulation of a public health program with multiapproach strategy, including education about the anticipated genetic consequences, prenatal diagnosis, neonatal screening, and genetic counseling, is a necessity.