| 1. |
- Henstrom, M., et al.
(author)
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Functional variants in the sucrase-isomaltase gene associate with increased risk of irritable bowel syndrome
- 2018
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In: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 67:2, s. 263-270
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Journal article (peer-reviewed)abstract
- Objective IBS is a common gut disorder of uncertain pathogenesis. Among other factors, genetics and certain foods are proposed to contribute. Congenital sucraseisomaltase deficiency (CSID) is a rare genetic form of disaccharide malabsorption characterised by diarrhoea, abdominal pain and bloating, which are features common to IBS. We tested sucrase-isomaltase (SI) gene variants for their potential relevance in IBS. Design We sequenced SI exons in seven familial cases, and screened four CSID mutations (p.Val557Gly, p. Gly1073Asp, p.Arg1124Ter and p.Phe1745Cys) and a common SI coding polymorphism (p.Val15Phe) in a multicentre cohort of 1887 cases and controls. We studied the effect of the 15Val to 15Phe substitution on SI function in vitro. We analysed p.Val15Phe genotype in relation to IBS status, stool frequency and faecal microbiota composition in 250 individuals from the general population. Results CSID mutations were more common in patients than asymptomatic controls (p=0.074; OR=1.84) and Exome Aggregation Consortium reference sequenced individuals (p=0.020; OR=1.57). 15Phe was detected in 6/7 sequenced familial cases, and increased IBS risk in case-control and population-based cohorts, with best evidence for diarrhoea phenotypes (combined p=0.00012; OR=1.36). In the population-based sample, 15Phe allele dosage correlated with stool frequency (p=0.026) and Parabacteroides faecal microbiota abundance (p=0.0024). The SI protein with 15Phe exhibited 35% reduced enzymatic activity in vitro compared with 15Val (p<0.05). Conclusions SI gene variants coding for disaccharidases with defective or reduced enzymatic activity predispose to IBS. This may help the identification of individuals at risk, and contribute to personalising treatment options in a subset of patients.
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| 2. |
- Assadi, G., et al.
(author)
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LACC1 polymorphisms in inflammatory bowel disease and juvenile idiopathic arthritis
- 2016
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In: Genes and Immunity. - : Nature Publishing Group. - 1466-4879 .- 1476-5470. ; 17:4, s. 261-264
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Journal article (peer-reviewed)abstract
- The function of the Laccase domain-containing 1 (LACC1) gene is unknown, but genetic variation at this locus has been reported to consistently affect the risk of Crohn's disease (CD) and leprosy. Recently, a LACC1 missense mutation was found in patients suffering from monogenic forms of CD, but also systemic juvenile idiopathic arthritis. We tested the hypothesis that LACC1 single nucleotide polymorphisms (SNPs), in addition to CD, are associated with juvenile idiopathic arthritis (JIA, non-systemic), and another major form of inflammatory bowel disease, ulcerative colitis (UC). We selected 11 LACC1 tagging SNPs, and tested their effect on disease risk in 3855 Swedish individuals from three case-control cohorts of CD, UC and JIA. We detected false discovery rate corrected significant associations with individual markers in all three cohorts, thereby expanding previous results for CD also to UC and JIA. LACC1's link to several inflammatory diseases suggests a key role in the human immune system and justifies further characterization of its function(s).
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| 3. |
- Bonfiglio, F., et al.
(author)
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Female-Specific Association Between Variants on Chromosome 9 and Self-Reported Diagnosis of Irritable Bowel Syndrome
- 2018
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In: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 155:1, s. 168-179
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Journal article (peer-reviewed)abstract
- BACKGROUND & AIMS: Genetic factors are believed to affect risk for irritable bowel syndrome (IBS), but there have been no sufficiently powered and adequately sized studies. To identify DNA variants associated with IBS risk, we performed a genome-wide association study (GWAS) of the large UK Biobank population-based cohort, which includes genotype and health data from 500,000 participants. METHODS: We studied 7,287,191 high-quality single nucleotide polymorphisms in individuals who self-reported a doctor's diagnosis of IBS (cases; n = 9576) compared to the remainder of the cohort (controls; n = 336,499) (mean age of study subjects, 40-69 years). Genome-wide significant findings were further investigated in 2045 patients with IBS from tertiary centers and 7955 population controls from Europe and the United States, and a small general population sample from Sweden (n = 249). Functional annotation of GWAS results was carried out by integrating data from multiple biorepositories to obtain biological insights from the observed associations. RESULTS: We identified a genome-wide significant association on chromosome 9q31.2 (single nucleotide polymorphism rs10512344; P = 3.57 x 10(-8)) in a region previously linked to age at menarche, and 13 additional loci of suggestive significance (P < 5.0 x 10(-6)). Sex-stratified analyses revealed that the variants at 9q31.2 affect risk of IBS in women only (P = 4.29 x 10(-10) in UK Biobank) and also associate with constipation-predominant IBS in women (P = .015 in the tertiary cohort) and harder stools in women (P = .0012 in the population-based sample). Functional annotation of the 9q31.2 locus identified 8 candidate genes, including the elongator complex protein 1 gene (ELP1 or IKB-KAP), which is mutated in patients with familial dysautonomia. CONCLUSIONS: In a sufficiently powered GWAS of IBS, we associated variants at the locus 9q31.2 with risk of IBS in women. This observation may provide additional rationale for investigating the role of sex hormones and autonomic dysfunction in IBS.
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| 4. |
- Boskabadi, Arman, et al.
(author)
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Carbonation of ophiolitic ultramafic rocks : Listvenite formation in the Late Cretaceous ophiolites of eastern Iran
- 2020
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In: Lithos. - : Elsevier BV. - 0024-4937 .- 1872-6143. ; 352–353
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Journal article (peer-reviewed)abstract
- Late Cretaceous mantle peridotite of the Birjand ophiolite (eastern Iran) contains variably serpentinized and carbonated/listvenitized rocks. Transformation from harzburgite protolith to final listvenite (quartz + magnesite/+/- dolomite + relict Cr-spinel) reflects successive fluid-driven reactions, the products of which are preserved in outcrop. Transformation of harzburgite to listvenite starts with lizardite serpentinization, followed by contemporaneous carbonation and antigorite serpentinization, antigorite-talc-magnesite alteration, finally producing listvenite where alteration is most pervasive. The spectrum of listvenitic assemblages includes silica-carbonate, carbonate and silica listvenites with the latter (also known as birbirite) being the youngest, based on crosscutting relationships. The petrological observations and mineral assemblages suggest hydrothermal fluids responsible for the lizardite serpentinization had low aCO(2), oxygen and sulfur fugacities, distinct from those causing antigorite serpentinization and carbonation/listvenitization, which had higher aCO(2), aSiO(2), and oxygen and sulfur fugacities. The carbonate and silica listvenite end-members indicate variations in aSiO(2) and aCO(2) of the percolating hydrothermal fluids, most likely driven by local variations in pH and temperature. Beyond the addition of H2O, serpentinization did not significantly redistribute major elements. Progressive infiltration of CO2-rich fluids and consequent carbonation segregated Mg into carbonate and Si into silica listvenites. Trace element mobility resulted in different enrichments of fluid-mobile, high field strength, and light rare earth elements in listvenites, indicating a listvenite mobility sequence. The delta C-13, delta O-18 and Sr-87/Sr-88 values of magnesite and dolomite in carbonated lithologies and veins point to sedimentary carbonate as the main C source. Fluid-mobile element (e.g., As and Sb) patterns in carbonated lithologies are consistent with contribution of subducted sediments in a forearc setting, suggesting sediment-derived fluids. Such fluids were produced by expulsion of pore fluids and release of structurally bound fluid from carbonate-bearing sediments in the Sistan Suture Zone (SsSZ) accretionary complex at shallow parts of mantle wedge. The CO2 -bearing fluids migrated up along the slab-mantle interface and circulated through the suture zone faults to be sequestered in mantle peridotites with marked element mobility signatures.
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| 6. |
- Fereshtehnejad, SM, et al.
(author)
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Comparison of the Psychological Symptoms and Disease-Specific Quality of Life between Early- and Typical-Onset Parkinson's Disease Patients
- 2014
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In: Parkinson's disease. - : Hindawi Limited. - 2090-8083 .- 2042-0080. ; 2014, s. 819260-
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Journal article (peer-reviewed)abstract
- The impact of Parkinson’s disease (PD) on psychological status and quality of life (QoL) may vary depending on age of disease onset. The aim of this study was to compare psychological symptoms and disease-specific QoL between early onset versus the rest of the PD patients. A total number of 140 PD patients with the mean current age of 61.3(SD=10.4) yr were recruited in this study. PD patients with the onset age of ≤50 yr were defined as “early-onset” (EOPD) group(n=45), while the ones with >50 yr at the time of diagnosis were categorized as the “typical-onset” (TOPD) patients(n=95). Different questionnaires and scales were used for between-group comparisons including PDQ39, HADS (hospital anxiety and depression scale), FSS (fatigue severity scale), MNA (mininutritional assessment), and the UPDRS. Depression score was significantly higher in EOPD group (6.3(SD=4.5)versus 4.5(SD=4.2),P=0.02). Among different domains of QoL, emotion score was also significantly higher in the EOPD group (32.3(SD=21.6)versus 24.4(SD=22.7),P=0.05). Our findings showed more severe depression and more impaired emotional domain of QoL in early-onset PD patients. Depression and anxiety play an important role to worsen QoL among both EOPD and TOPD patients, while no interaction was observed in the efficacy of these two psychiatric symptoms and the onset age of PD patients.
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| 7. |
- Fereshtehnejad, SM, et al.
(author)
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Cross-cultural validity, reliability, and psychometric properties of the persian version of the scales for outcomes in Parkinson's disease-psychosocial questionnaire
- 2014
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In: Neurology research international. - : Hindawi Limited. - 2090-1852 .- 2090-1860. ; 2014, s. 260684-
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Journal article (peer-reviewed)abstract
- Objectives. Considering the influence of different motor and nonmotor features of Parkinson’s disease (PD), it is important to evaluate the psychosocial functioning of the patients. For this purpose, the scales for outcomes in Parkinson’s disease-psychosocial questionnaire (SCOPA-PS) has been previously designed. The aim of our study was to assess the cross-cultural validation and psychometric properties of the Persian version of the SCOPA-PS.Methods. One hundred and ten nondemented idiopathic Parkinson’s disease (IPD) patients were consecutively recruited from an outpatient referral movement disorder clinic. Eligible patients filled up a number of questionnaires including the Persian version of SCOPA-PS during the face-to-face interview session and clinical examination to measure disease severity, nonmotor psychiatric symptoms, and health-related quality of life (HRQoL).Results. The highest and lowest correlation coefficients of internal consistency were reported for item 7 on “asking for help”(r=0.765)and item 5 on “sexual problems”(r=0.553). Cronbach’s alpha reliability coefficient of the entire scale was 0.87 (95% CI: 0.83–0.90). The Hoehn and Yahr stage(r=0.34, P<0.001), Schwab and England ADL scale(r=-0.55, P<0.001), anxiety(r=0.64, P<0.001), depression(r=0.71, P<0.001), and fatigue(r=0.35, P<0.001)were significantly correlated with the total score of the SCOPA-PS questionnaire.Conclusions. The Persian version of SCOPA-PS is a highly reliable and valid scale to measure psychosocial functioning in IPD patients with different sex, age-group, and educational level, which could be applied in future researches. Disease severity scales, depression, anxiety, fatigue, and different domains of HRQoL were all associated with psychosocial functioning in PD patients.
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