SLCO5A1 and synaptic assembly genes contribute to impulsivity in juvenile myoclonic epilepsy.

Elevated impulsivity is a key component of attention-deficit hyperactivity disorder (ADHD), bipolar disorder and juvenile myoclonic epilepsy (JME). We performed a genome-wide association, colocalization, polygenic risk score, and pathway analysis of impulsivity in JME (n = 381). Results were followed up with functional characterisation using a drosophila model. We identified genome-wide associated SNPs at 8q13.3 (P = 7.5 × 10-9) and 10p11.21 (P = 3.6 × 10-8). The 8q13.3 locus colocalizes with SLCO5A1 expression quantitative trait loci in cerebral cortex (P = 9.5 × 10-3). SLCO5A1 codes for an organic anion transporter and upregulates synapse assembly/organisation genes. Pathway analysis demonstrates 12.7-fold enrichment for presynaptic membrane assembly genes (P = 0.0005) and 14.3-fold enrichment for presynaptic organisation genes (P = 0.0005) including NLGN1 and PTPRD. RNAi knockdown of Oatp30B, the Drosophila polypeptide with the highest homology to SLCO5A1, causes over-reactive startling behaviour (P = 8.7 × 10-3) and increased seizure-like events (P = 6.8 × 10-7). Polygenic risk score for ADHD genetically correlates with impulsivity scores in JME (P = 1.60 × 10-3). SLCO5A1 loss-of-function represents an impulsivity and seizure mechanism. Synaptic assembly genes may inform the aetiology of impulsivity in health and disease.

Investigating the association between fasting insulin, erythrocytosis and HbA1c through Mendelian randomization and observational analyses.

Background: Insulin resistance (IR) with associated compensatory hyperinsulinemia (HI) are early abnormalities in the etiology of prediabetes (preT2D) and type 2 diabetes (T2D). IR and HI also associate with increased erythrocytosis. Hemoglobin A1c (HbA1c) is commonly used to diagnose and monitor preT2D and T2D, but can be influenced by erythrocytosis independent of glycemia. Methods: We undertook bidirectional Mendelian randomization (MR) in individuals of European ancestry to investigate potential causal associations between increased fasting insulin adjusted for BMI (FI), erythrocytosis and its non-glycemic impact on HbA1c. We investigated the association between the triglyceride-glucose index (TGI), a surrogate measure of IR and HI, and glycation gap (difference between measured HbA1c and predicted HbA1c derived from linear regression of fasting glucose) in people with normoglycemia and preT2D. Results: Inverse variance weighted MR (IVWMR) suggested that increased FI increases hemoglobin (Hb, b=0.54 ± 0.09, p=2.7 x 10-10), red cell count (RCC, b=0.54 ± 0.12, p=5.38x10-6) and reticulocyte (RETIC, b=0.70 ± 0.15, p=2.18x10-6). Multivariable MR indicated that increased FI did not impact HbA1c (b=0.23 ± 0.16, p=0.162) but reduced HbA1c after adjustment for T2D (b=0.31 ± 0.13, p=0.016). Increased Hb (b=0.03 ± 0.01, p=0.02), RCC (b=0.02 ± 0.01, p=0.04) and RETIC (b=0.03 ± 0.01, p=0.002) might modestly increase FI. In the observational cohort, increased TGI associated with decreased glycation gap, (i.e., measured HbA1c was lower than expected based on fasting glucose, (b=-0.09 ± 0.009, p<0.0001)) in people with preT2D but not in those with normoglycemia (b=0.02 ± 0.007, p<0.0001). Conclusions: MR suggests increased FI increases erythrocytosis and might potentially decrease HbA1c by non-glycemic effects. Increased TGI, a surrogate measure of increased FI, associates with lower-than-expected HbA1c in people with preT2D. These findings merit confirmatory studies to evaluate their clinical significance.

Association Between Obesity and Chronic Kidney Disease: Multivariable Mendelian Randomization Analysis and Observational Data From a Bariatric Surgery Cohort.

Obesity is postulated to independently increase chronic kidney disease (CKD), even after adjusting for type 2 diabetes (T2D) and hypertension. Dysglycemia below T2D thresholds, frequently seen with obesity, also increases CKD risk. Whether obesity increases CKD independent of dysglycemia and hypertension is unknown and likely influences the optimal weight loss (WL) needed to reduce CKD. T2D remission rates plateau with 20-25% WL after bariatric surgery (BS), but further WL increases normoglycemia and normotension. We undertook bidirectional inverse variance weighted Mendelian randomization (IVWMR) to investigate potential independent causal associations between increased BMI and estimated glomerular filtration rate (eGFR) in CKD (CKDeGFR) (<60 mL/min/1.73 m2) and microalbuminuria (MA). In 5,337 BS patients, we assessed whether WL influences >50% decline in eGFR (primary outcome) or CKD hospitalization (secondary outcome), using <20% WL as a comparator. IVWMR results suggest that increased BMI increases CKDeGFR (b = 0.13, P = 1.64 × 10-4; odds ratio [OR] 1.14 [95% CI 1.07, 1.23]) and MA (b = 0.25; P = 2.14 × 10-4; OR 1.29 [1.13, 1.48]). After adjusting for hypertension and fasting glucose, increased BMI did not significantly increase CKDeGFR (b = -0.02; P = 0.72; OR 0.98 [0.87, 1.1]) or MA (b = 0.19; P = 0.08; OR 1.21 [0.98, 1.51]). Post-BS WL significantly reduced the primary outcome with 30 to <40% WL (hazard ratio [HR] 0.53 [95% CI 0.32, 0.87]) but not 20 to <30% WL (HR 0.72 [0.44, 1.2]) and ≥40% WL (HR 0.73 [0.41, 1.30]). For CKD hospitalization, progressive reduction was seen with increased WL, which was significant for 30 to <40% WL (HR 0.37 [0.17, 0.82]) and ≥40% WL (HR 0.24 [0.07, 0.89]) but not 20 to <30% WL (HR 0.60 [0.29, 1.23]). The data suggest that obesity is likely not an independent cause of CKD. WL thresholds previously associated with normotension and normoglycemia, likely causal mediators, may reduce CKD after BS.

DNA methylation mediates development of HbA1c-associated complications in type 1 diabetes.

Metabolic memory, the persistent benefits of early glycaemic control on preventing and/or delaying the development of diabetic complications, has been observed in the Diabetes Control and Complications Trial (DCCT) and in the Epidemiology of Diabetes Interventions and Complications (EDIC) follow-up study, but the underlying mechanisms remain unclear. Here, we show the involvement of epigenetic DNA methylation (DNAme) in metabolic memory by examining its associations with preceding glycaemic history, and with subsequent development of complications over an 18-yr period in the blood DNA of 499 randomly selected DCCT participants with type 1 diabetes who are also followed up in EDIC. We demonstrate the associations between DNAme near the closeout of DCCT and mean HbA1c during DCCT (mean-DCCT HbA1c) at 186 cytosine-guanine dinucleotides (CpGs) (FDR < 15%, including 43 at FDR < 5%), many of which were located in genes related to complications. Exploration studies into biological function reveal that these CpGs are enriched in binding sites for the C/EBP transcription factor, as well as enhancer/transcription regions in blood cells and haematopoietic stem cells, and open chromatin states in myeloid cells. Mediation analyses show that, remarkably, several CpGs in combination explain 68-97% of the association of mean-DCCT HbA1c with the risk of complications during EDIC. In summary, DNAme at key CpGs appears to mediate the association between hyperglycaemia and complications in metabolic memory, through modifying enhancer activity at myeloid and other cells.

DNA methylation age calculators reveal association with diabetic neuropathy in type 1 diabetes.

BACKGROUND: Many CpGs become hyper or hypo-methylated with age. Multiple methods have been developed by Horvath et al. to estimate DNA methylation (DNAm) age including Pan-tissue, Skin & Blood, PhenoAge, and GrimAge. Pan-tissue and Skin & Blood try to estimate chronological age in the normal population whereas PhenoAge and GrimAge use surrogate markers associated with mortality to estimate biological age and its departure from chronological age. Here, we applied Horvath's four methods to calculate and compare DNAm age in 499 subjects with type 1 diabetes (T1D) from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study using DNAm data measured by Illumina EPIC array in the whole blood. Association of the four DNAm ages with development of diabetic complications including cardiovascular diseases (CVD), nephropathy, retinopathy, and neuropathy, and their risk factors were investigated. RESULTS: Pan-tissue and GrimAge were higher whereas Skin & Blood and PhenoAge were lower than chronological age (p < 0.0001). DNAm age was not associated with the risk of CVD or retinopathy over 18-20 years after DNAm measurement. However, higher PhenoAge (ß = 0.023, p = 0.007) and GrimAge (ß = 0.029, p = 0.002) were associated with higher albumin excretion rate (AER), an indicator of diabetic renal disease, measured over time. GrimAge was also associated with development of both diabetic peripheral neuropathy (OR = 1.07, p = 9.24E-3) and cardiovascular autonomic neuropathy (OR = 1.06, p = 0.011). Both HbA1c (ß = 0.38, p = 0.026) and T1D duration (ß = 0.01, p = 0.043) were associated with higher PhenoAge. Employment (ß = - 1.99, p = 0.045) and leisure time (ß = - 0.81, p = 0.022) physical activity were associated with lower Pan-tissue and Skin & Blood, respectively. BMI (ß = 0.09, p = 0.048) and current smoking (ß = 7.13, p = 9.03E-50) were positively associated with Skin & Blood and GrimAge, respectively. Blood pressure, lipid levels, pulse rate, and alcohol consumption were not associated with DNAm age regardless of the method used. CONCLUSIONS: Various methods of measuring DNAm age are sub-optimal in detecting people at higher risk of developing diabetic complications although some work better than the others.

Association of IGF1 and VEGFA polymorphisms with diabetic retinopathy in Pakistani population.

AIMS: The incidence of microvascular complications, including diabetic retinopathy (DR), increases with duration of type 2 diabetes (T2D). Meta-GWAS have reported numerous single-nucleotide polymorphisms (SNPs) associated with T2D; however, no loci, achieving genome-wide significance has been reported for DR. Vascular endothelial growth factor A (VEGFA) and insulin-like growth factor 1 (IGF1) are considered as potential genetic candidates involved in T2D and DR progression. Moreover, the association of serum levels of these proteins with diabetes-related traits is controversial. Therefore, the current study was designed to evaluate the possible genetic predisposition and role of these circulating growth factors in serum in the pathophysiology of T2D and DR. METHODS: A cohort of 1126 individuals with T2D was collected including those without retinopathy (DNR = 573), non-progressive diabetic retinopathy (NPDR = 301) and progressive diabetic retinopathy (PDR = 252), and 348 healthy controls. Genomic DNA was isolated, and six SNPs: rs833061, rs13207351, rs1570360, rs2010963, rs5742632 and rs6214, were genotyped and results statistically analyzed. ELISA was performed on a subset of the samples to measure serum levels of IGF1 and VEGFA. RESULTS: The minor allele of rs6214 was associated with T2D [OR = 1.67 (95% CI 1.39-2.01, p = 4.9E-8)], rs13207351 was associated with NPDR [OR = 1.97 (95% CI 1.28-3.03, p = 9.0E-3)]when compared with DNR, and rs5742632 showed positive association with PDR [OR = 1.66 (95% CI 1.33-2.05, p = 1.0E-4)] compared to DNR. Lowered IGF1 serum levels were found to be associated with T2D, NPDR and PDR. CONCLUSIONS: IGF1 was found to increase the T2DM susceptibility as well as advanced DR, i.e., PDR, while VEGFA was found to be associated with early DR stage, i.e., NPDR.

New Locus for Skin Intrinsic Fluorescence in Type 1 Diabetes Also Associated With Blood and Skin Glycated Proteins.

Skin fluorescence (SF) noninvasively measures advanced glycation end products (AGEs) in the skin and is a risk indicator for diabetes complications. N-acetyltransferase 2 (NAT2) is the only known locus influencing SF. We aimed to identify additional genetic loci influencing SF in type 1 diabetes (T1D) through a meta-analysis of genome-wide association studies (N = 1,359) including Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) and Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR). A locus on chromosome 1, rs7533564 (P = 1.9 × 10(-9)), was associated with skin intrinsic fluorescence measured by SCOUT DS (excitation 375 nm, emission 435-655 nm), which remained significant after adjustment for time-weighted HbA1c (P = 1.7 × 10(-8)). rs7533564 was associated with mean HbA1c in meta-analysis (P = 0.0225), mean glycated albumin (P = 0.0029), and glyoxal hydroimidazolones (P = 0.049), an AGE measured in skin biopsy collagen, in DCCT. rs7533564 was not associated with diabetes complications in DCCT/EDIC or with SF in subjects without diabetes (nondiabetic [ND]) (N = 8,721). In conclusion, we identified a new locus associated with SF in T1D subjects that did not show similar effect in ND subjects, suggesting a diabetes-specific effect. This association needs to be investigated in type 2 diabetes.

Association of granulomatosis with polyangiitis (Wegener's) with HLA-DPB1*04 and SEMA6A gene variants: evidence from genome-wide analysis.

OBJECTIVE: To identify genetic determinants of granulomatosis with polyangiitis (Wegener's) (GPA). METHODS: We carried out a genome-wide association study (GWAS) of 492 GPA cases and 1,506 healthy controls (white subjects of European descent), followed by replication analysis of the most strongly associated signals in an independent cohort of 528 GPA cases and 1,228 controls. RESULTS: Genome-wide significant associations were identified in 32 single-nucleotide polymorphic (SNP) markers across the HLA region, the majority of which were located in the HLA-DPB1 and HLA-DPA1 genes encoding the class II major histocompatibility complex (MHC) DPß chain 1 and DPα chain 1 proteins, respectively. Peak association signals in these 2 genes, emanating from SNPs rs9277554 (for DPß chain 1) and rs9277341 (DPα chain 1) were strongly replicated in an independent cohort (in the combined analysis of the initial cohort and the replication cohort, P = 1.92 × 10(-50) and 2.18 × 10(-39) , respectively). Imputation of classic HLA alleles and conditional analyses revealed that the SNP association signal was fully accounted for by the classic HLA-DPB1*04 allele. An independent single SNP, rs26595, near SEMA6A (the gene for semaphorin 6A) on chromosome 5, was also associated with GPA, reaching genome-wide significance in a combined analysis of the GWAS and replication cohorts (P = 2.09 × 10(-8) ). CONCLUSION: We identified the SEMA6A and HLA-DP loci as significant contributors to risk for GPA, with the HLA-DPB1*04 allele almost completely accounting for the MHC association. These two associations confirm the critical role of immunogenetic factors in the development of GPA.

Meta-analysis of genetic polymorphisms in granulomatosis with polyangiitis (Wegener's) reveals shared susceptibility loci with rheumatoid arthritis.

OBJECTIVE: To examine the association of previously identified autoimmune disease susceptibility loci with granulomatosis with polyangiitis (Wegener's) (GPA), and to determine whether the genetic susceptibility profiles of other autoimmune diseases are associated with those of GPA. METHODS: Genetic data from 2 cohorts were meta-analyzed. Genotypes for 168 previously identified single-nucleotide polymorphisms (SNPs) associated with susceptibility to different autoimmune diseases were ascertained in a total of 880 patients with GPA and 1,969 control subjects of European descent. Single-marker associations were identified using additive logistic regression models. Associations of multiple SNPs with GPA were assessed using genetic risk scores based on susceptibility loci for Crohn's disease, type 1 diabetes, systemic lupus erythematosus, rheumatoid arthritis (RA), celiac disease, and ulcerative colitis. Adjustment for population substructure was performed in all analyses, using ancestry-informative markers and principal components analysis. RESULTS: Genetic polymorphisms in CTLA4 were significantly associated with GPA in the single-marker meta-analysis (odds ratio [OR] 0.79, 95% confidence interval [95% CI] 0.70-0.89, P = 9.8 × 10(-5) ). The genetic risk score for RA susceptibility markers was significantly associated with GPA (OR 1.05 per 1-unit increase in genetic risk score, 95% CI 1.02-1.08, P = 5.1 × 10(-5) ). CONCLUSION: RA and GPA may arise from a similar genetic predisposition. Aside from CTLA4, other loci previously found to be associated with common autoimmune diseases were not statistically significantly associated with GPA in this study.

Influence of polymorphisms in the RANKL/RANK/OPG signaling pathway on volumetric bone mineral density and bone geometry at the forearm in men.

We sought to determine the influence of single-nucleotide polymorphisms (SNPs) in RANKL, RANK, and OPG on volumetric bone mineral density (vBMD) and bone geometry at the radius in men. Pairwise tag SNPs (r (2) ≥ 0.8) for RANKL (n = 8), RANK (n = 44), and OPG (n = 22) and five SNPs near RANKL and OPG strongly associated with areal BMD in genomewide association studies were previously genotyped in men aged 40-79 years in the European Male Ageing Study (EMAS). Here, these SNPs were analyzed in a subsample of men (n = 589) who had peripheral quantitative computed tomography (pQCT) performed at the distal (4%) and mid-shaft (50%) radius. Estimated parameters were total and trabecular vBMD (mg/mm(3)) and cross-sectional area (mm(2)) at the 4% site and cortical vBMD (mg/mm(3)); total, cortical, and medullary area (mm(2)); cortical thickness (mm); and stress strain index (SSI) (mm(3)) at the 50% site. We identified 12 OPG SNPs associated with vBMD and/or geometric parameters, including rs10505348 associated with total vBMD (ß [95% CI] = 9.35 [2.12-16.58], P = 0.011), cortical vBMD (ß [95% CI] = 5.62 [2.10-9.14], P = 0.002), cortical thickness (ß [95% CI] = 0.08 [0.03-0.13], P = 0.002), and medullary area (ß [95% CI] = -2.90 [-4.94 to -0.86], P = 0.005) and rs2073618 associated with cortical vBMD (ß [95% CI] = -4.30 [-7.78 to -0.82], P = 0.015) and cortical thickness (ß [95% CI] = -0.08 [-0.13 to -0.03], P = 0.001). Three RANK SNPs were associated with vBMD, including rs12956925 associated with trabecular vBMD (ß [95% CI] = -7.58 [-14.01 to -1.15], P = 0.021). There were five RANK SNPs associated with geometric parameters, including rs8083511 associated with distal radius cross-sectional area (ß [95% CI] = 8.90 [0.92-16.88], P = 0.029). No significant association was observed between RANKL SNPs and pQCT parameters. Our findings suggest that genetic variation in OPG and RANK influences radius vBMD and geometry in men.

Genetic variation in the RANKL/RANK/OPG signaling pathway is associated with bone turnover and bone mineral density in men.

The aim of this study was to determine if single-nucleotide polymorphisms (SNPs) in RANKL, RANK, and OPG influence bone turnover and bone mineral density (BMD) in men. Pairwise tag SNPs (r(2) > or = 0.8) were selected for RANKL, RANK, and OPG and their 10-kb flanking regions. Selected tag SNPs plus five SNPs near RANKL and OPG, associated with BMD in published genome-wide association studies (GWAS), were genotyped in 2653 men aged 40 to 79 years of age recruited for participation in a population-based study of male aging, the European Male Ageing Study (EMAS). N-terminal propeptide of type I procollagen (PINP) and C-terminal cross-linked telopeptide of type I collagen (CTX-I) serum levels were measured in all men. BMD at the calcaneus was estimated by quantitative ultrasound (QUS) in all men. Lumbar spine and total-hip areal BMD (BMD(a)) was measured by dual-energy X-ray absorptiometry (DXA) in a subsample of 620 men. Multiple OPG, RANK, and RANKL SNPs were associated with bone turnover markers. We also identified a number of SNPs associated with BMD, including rs2073618 in OPG and rs9594759 near RANKL. The minor allele of rs2073618 (C) was associated with higher levels of both PINP (beta = 1.83, p = .004) and CTX-I (beta = 17.59, p = 4.74 x 10(-4)), and lower lumbar spine BMD(a) (beta = -0.02, p = .026). The minor allele of rs9594759 (C) was associated with lower PINP (beta = -1.84, p = .003) and CTX-I (beta = -27.02, p = 6.06 x 10(-8)) and higher ultrasound BMD at the calcaneus (beta = 0.01, p = .037). Our findings suggest that genetic variation in the RANKL/RANK/OPG signaling pathway influences bone turnover and BMD in European men.

Mechanisms controlling anaemia in Trypanosoma congolense infected mice.

BACKGROUND: Trypanosoma congolense are extracellular protozoan parasites of the blood stream of artiodactyls and are one of the main constraints on cattle production in Africa. In cattle, anaemia is the key feature of disease and persists after parasitaemia has declined to low or undetectable levels, but treatment to clear the parasites usually resolves the anaemia. METHODOLOGY/PRINCIPAL FINDINGS: The progress of anaemia after Trypanosoma congolense infection was followed in three mouse strains. Anaemia developed rapidly in all three strains until the peak of the first wave of parasitaemia. This was followed by a second phase, characterized by slower progress to severe anaemia in C57BL/6, by slow recovery in surviving A/J and a rapid recovery in BALB/c. There was no association between parasitaemia and severity of anaemia. Furthermore, functional T lymphocytes are not required for the induction of anaemia, since suppression of T cell activity with Cyclosporin A had neither an effect on the course of infection nor on anaemia. Expression of genes involved in erythropoiesis and iron metabolism was followed in spleen, liver and kidney tissues in the three strains of mice using microarrays. There was no evidence for a response to erythropoietin, consistent with anaemia of chronic disease, which is erythropoietin insensitive. However, the expression of transcription factors and genes involved in erythropoiesis and haemolysis did correlate with the expression of the inflammatory cytokines Il6 and Ifng. CONCLUSIONS/SIGNIFICANCE: The innate immune response appears to be the major contributor to the inflammation associated with anaemia since suppression of T cells with CsA had no observable effect. Several transcription factors regulating haematopoiesis, Tal1, Gata1, Zfpm1 and Klf1 were expressed at consistently lower levels in C57BL/6 mice suggesting that these mice have a lower haematopoietic capacity and therefore less ability to recover from haemolysis induced anaemia after infection.

A web-based patient education system and self-help group in Persian language for inflammatory bowel disease patients.

BACKGROUND AND AIMS: To study the use patterns of a Persian web-based patient education system for inflammatory bowel disease (IBD) patients in Iran. METHODS: A web-based patient education system was developed with Persian content in three sections: general, ulcerative colitis (UC), and Crohn's disease (CD). The website included a forum for patients to communicate as a self-help group. A customized web tracking system recorded web use statistics. Polls at the bottom of each page collected the visitors' opinion on the extent of helpfulness and readability of page contents. Web use data were analyzed for an 18-month period from October 2004 to April 2006. RESULTS: Having excluded page visits from search engine robots, the website's homepage was visited 4452 times (mean of monthly visits: 234, range: 102-330). The web pages titled Anatomy of gastrointestinal system, Nutrition in IBD, Diagnostic tests, How to cope with IBD, and IBD in women were the most favorite in general section. The web page titled IBD treatment was the most visited in both CD and UC sections followed by the web pages on cause of disease, diagnostic procedures and complications in CD section; and those titled symptoms, cause of disease and risk factors in the UC section. Overall, the content evaluation polls received 294 hits (from 186 unique visitors) of which, 196 (67%) were from patients, 30 (10%) from patients' relatives/friends, 21 (7%) from doctors, and 47 (16%) from other groups. During the 18-month period, 47 patients registered in the self-help forum, 24 threads were opened, and 97 posts (33 in CD and 64 in UC section) were sent. CONCLUSIONS: Considering the increasing trend of Internet use in developing countries like Iran, and the consequent increase in the proportion of Internet-using patients, and finally the time constraints gastroenterologists face answering patients' questions; similar websites seem to be effective ways of patient education in close future.

High prevalence of reflux oesophagitis among upper endoscopies of Iranian patients.

BACKGROUND AND AIM: To reinvestigate the prevalence of reflux esophagitis among upper endoscopies in a series of Iranian patients, considering the high prevalence of reflux esophagitis (76%) reported by an earlier Iranian study and the scanty data regarding prevalence of gastroesophageal reflux disease from Iran and the Middle East. METHODS: Patients referred for upper endoscopy to an outpatient gastroenterology clinic in Tehran (May 2005-January 2006) were interviewed using a questionnaire before endoscopy. Gastroesophageal reflux disease was defined as having any degree of reflux esophagitis on endoscopy, or having heartburn or regurgitation on a weekly basis during the preceding 3 months. Reflux esophagitis was diagnosed and graded using Los Angeles classification. Check-up patients were excluded. Gastroesophageal reflux disease, nonerosive reflux disease, and reflux esophagitis groups were compared with non-gastroesophageal reflux disease patients with regard to the following factors: sex, age, body mass index (BMI), hiatus hernia, smoking, alcohol use, and level of education. RESULTS: Out of 501 consecutive patients undergoing upper endoscopy (195 men, 306 women; mean+/-SD of age, 44.7+/-15 years; mean+/-SD of BMI, 24.9+/-4.4), 50 and 48% had reflux esophagitis with and without exclusion of the patients on acid-suppressing drugs in the past 2 weeks, respectively. Most had grade A (90%) or B (9%) reflux esophagitis. Only one patient (0.2%) had Barrett's esophagus. By Rome-II criteria, 116 had dyspepsia symptoms (predominant), of whom 41% had reflux esophagitis. High BMI (>25) and hiatus hernia both showed statistically significant associations with gastroesophageal reflux disease, whereas nonerosive reflux disease and reflux esophagitis were associated only with high BMI and hiatus hernia, respectively. Although the nonerosive reflux disease patients were of a lower education level than non-gastroesophageal reflux disease patients, no significant association of education level with gastroesophageal reflux disease and reflux esophagitis was found. CONCLUSION: This study showed a significantly higher prevalence of reflux esophagitis among Iranian upper-endoscopy outpatients compared with the findings of non-Iranian studies.

Symptom patterns and relative distribution of functional bowel disorders in 1,023 gastroenterology patients in Iran.

BACKGROUND AND AIMS: There are scanty data on functional bowel disorder (FBD) patterns in Iran. This first-time study tried to provide preliminary data on relative distribution of different types of FBD and their symptom patterns in Iranian patients. METHODS: A consecutive sample of 1,023 patients in an outpatient gastroenterology clinic in central Tehran was interviewed using two questionnaires based on Rome II criteria from December 2004 to May 2005 to detect FBD patients. RESULTS: Of 1,023 gastroenterology patients, 410 met Rome II criteria for FBD; functional constipation, 115 (28%); irritable bowel syndrome (IBS), 110 (27%) [IBS-C, 29%; IBS-D, 11%; IBS-A, 60%]; functional bloating, 102 (25%); unspecified FBD, 76 (18%); and functional diarrhea, 7 (2%). FBD had no association with age or level of education, while it was more frequent in women (P=0.001). FBD was also more frequent among those with a history of abdominal/pelvic surgery (P=0.021). IBS patients had a lower mean of age compared with non-FBD group, while patients with constipation were older (Mann-Whitney U test, P=0.006). Constipation-related symptoms were the most frequent symptoms among IBS patients. Constipation (<3 defecations/week) was also the most frequent change in bowel habit in bloating and unspecified FBD patients. Fourteen percent of IBS consulters and 8.7% of functional constipation consulters met Rome II criteria for dyspepsia (disregarding the ruling out of upper gastrointestinal organic disease). Only 20% of patients with functional constipation were consulters. CONCLUSIONS: Population-based studies at provincial levels are essential to clarify FBD patterns in each provincial district in the country.

Knowledge of disease and health information needs of the patients with inflammatory bowel disease in a developing country.

BACKGROUND AND AIMS: This study was performed to have a first-time assessment on the knowledge level of a population of inflammatory bowel disease (IBD) patients in a developing country like Iran and to identify their health information preferences. METHODS: One hundred over 18-year-old IBD patients presenting to an outpatient gastroenterology clinic in Tehran from April to November 2004 were asked to complete Persian-translated version of 24-item Crohn's and Colitis Knowledge (CCKNOW) score questionnaire and an additional questionnaire collecting their favorite disease-related knowledge topics. RESULTS: All of the patients (64 females, 36 males) wished to know more about their disease. The cause of IBD and the medications were the most favorite knowledge topics. The mean and median of CCKNOW score of the patients was 4.65 and 4.0 (out of 24), respectively. Women showed significantly higher scores than men (p=0.006). There was also a weak positive correlation between the level of education and CCKNOW score (Spearman's rho=0.23, p=0.02). No significant correlation was found between age, duration of disease, self-estimated level of suffering from disease, and CCKNOW score. The most severe knowledge deficit was evident in knowledge on IBD complications. CONCLUSION: Despite the overt inclination of Iranian IBD patients to know more about their disease, their knowledge levels were significantly lower than the IBD patients in developed countries. The more profound knowledge deficit in IBD complications may lead to disastrous aftermaths such as late diagnosis of colorectal cancer induced by prolonged IBD. Vigorous patient education programs for the Iranian IBD patient are suggested focusing on areas of knowledge deficit and their favorite topics.

An economic analysis of premarriage prevention of hepatitis B transmission in Iran.

BACKGROUND: To assess the economic aspects of HBV (hepatitis B virus) transmission prevention for premarriage individuals in a country with cultural backgrounds like Iran and intermediate endemicity of HBV infection. METHODS: A cost-effectiveness analysis model was used from the health care system and society perspectives. The effectiveness was defined as the number of chronic HBV infections averted owing to one of the following strategies:1) HBsAg screening to find those would-be couples one of whom is HBsAg positive and putting seronegative subjects on a protection protocol comprising HBV vaccination, single dose HBIG and condom protection.2) HBsAg screening as above, in addition to performing HBcAb screening in the HBsAg negative spouses of the HBsAg positive persons and giving the protocol only to HBcAb negative ones.Sensitivity and threshold analyses were conducted. RESULTS: The cost of each chronic infection averted was 202$ and 197$ for the strategies 1 and 2, respectively. Sensitivity analysis showed that strategy 2 was always slightly cheaper than strategy 1. The discounted threshold value for the lifetime costs of chronic liver disease, above which the model was cost saving was 2818$ in strategy 1 and 2747$ in strategy 2. CONCLUSIONS: Though premarriage prevention of HBV transmission in the countries with cultural backgrounds similar to Iran seems cost saving, further studies determining precise costs of HBV infection in Iran can lead to a better analysis.