| 1. |
|
|
| 2. |
- Mondal, Tanmoy, 1981, et al.
(författare)
-
Sense-antisense lncRNA pair encoded by locus 6p22.3 determines neuroblastoma susceptibility via the USP36-CHD7-SOX9 regulatory axis
- 2018
-
Ingår i: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 33:3
-
Tidskriftsartikel (refereegranskat)abstract
- Trait-associated loci often map to genomic regions encoding long noncoding RNAs (lncRNAs), but the role of these lncRNAs in disease etiology is largely unexplored. We show that a pair of sense/antisense lncRNA (6p22lncRNAs) encoded by CASC15 and NBAT1 located at the neuroblastoma (NB) risk-associated 6p22.3 locus are tumor suppressors and show reduced expression in high-risk NBs. Loss of functional synergy between 6p22lncRNAs results in an undifferentiated state that is maintained by a gene-regulatory network, including SOX9 located on 17q, a region frequently gained in NB. 6p22lncRNAs regulate SOX9 expression by controlling CHD7 stability via modulating the cellular localization of USP36, encoded by another 17q gene. This regulatory nexus between 6p22.3 and 17q regions may lead to potential NB treatment strategies.
|
|
| 3. |
- Lindahl, Katarina, et al.
(författare)
-
Allele Dependent Silencing of Collagen Type I Using Small Interfering RNAs Targeting 3'UTR Indels : a Novel Therapeutic Approach in Osteogenesis Imperfecta
- 2013
-
Ingår i: International Journal of Medical Sciences. - : Ivyspring International Publisher. - 1449-1907. ; 10:10, s. 1333-1343
-
Tidskriftsartikel (refereegranskat)abstract
- Osteogenesis imperfecta, also known as "brittle bone disease", is a heterogeneous disorder of connective tissue generally caused by dominant mutations in the genes COL1A1 and COL1A2, encoding the α1 and α2 chains of type I (pro)collagen. Symptomatic patients are usually prescribed bisphosphonates, but this treatment is neither curative nor sufficient. A promising field is gene silencing through RNA interference. In this study small interfering RNAs (siRNAs) were designed to target each allele of 3'UTR insertion/deletion polymorphisms (indels) in COL1A1 (rs3840870) and COL1A2 (rs3917). For both indels, the frequency of heterozygous individuals was determined to be approximately 50% in Swedish cohorts of healthy controls as well as in patients with osteogenesis imperfecta. Cultures of primary human bone derived cells were transfected with siRNAs through magnet-assisted transfection. cDNA from transfected cells was sequenced in order to measure targeted allele/non-targeted allele ratios and the overall degree of silencing was assessed by quantitative PCR. Successful allele dependent silencing was observed, with promising results for siRNAs complementary to both the insertion and non-insertion harboring alleles. In COL1A1 cDNA the indel allele ratios were shifted from 1 to 0.09 and 0.19 for the insertion and non-insertion allele respectively while the equivalent resulting ratios for COL1A2 were 0.05 and 0.01. Reductions in mRNA abundance were also demonstrated; in cells treated with siRNAs targeting the COL1A1 alleles the average COL1A1 mRNA levels were reduced 65% and 78% compared to negative control levels and in cells treated with COL1A2 siRNAs the average COL1A2 mRNA levels were decreased 26% and 49% of those observed in the corresponding negative controls. In conclusion, allele dependent silencing of collagen type I utilizing 3'UTR indels common in the general population constitutes a promising mutation independent therapeutic approach for osteogenesis imperfecta.
|
|
| 4. |
- Karypidis, A.-H., et al.
(författare)
-
Deletion polymorphism of the UGT2B17 gene is associated with increased risk for prostate cancer and correlated to gene expression in the prostate
- 2008
-
Ingår i: The Pharmacogenomics Journal. - Avenet, NJ : Nature Pub. Group. - 1470-269X .- 1473-1150. ; 8:2, s. 147-151
-
Tidskriftsartikel (refereegranskat)abstract
- Metabolism of androgens includes glucuronidation, the major pathway of steroid elimination in several steroid target tissues. Glucuronidation is catalysed by UDP-glucuronosyltransferases (UGTs). UGT2B17 has been shown to be particularly active against androgens and is highly abundant in the prostate. Recently, we discovered that deletion of the UGT2B17 gene is associated with low or undetectable urinary testosterone levels. Here, we determined the phenotypic outcome of the deletion by quantifying the UGT2B17 mRNA expression in normal prostate tissues in individuals with different genotypes. Additionally, the frequency of UGT2B17 deletion polymorphism was studied in a Swedish population-based case–control study including 176 patients diagnosed with prostate cancer and 161 controls. We found that the individuals homozygous for the insertion allele expressed 30 times more UGT2B17 mRNA in prostate tissue than the heterozygotes. Carriers of the deletion allele had a significantly increased risk of prostate cancer (OR=2.07; 95% CI=1.32–3.25). In conclusion, these results show the UGT2B17 deletion polymorphism is associated with prostate cancer risk.
|
|
| 5. |
- Ali, Magdi M. M., et al.
(författare)
-
Fc gamma RIIa (CD32) polymorphism and onchocercal skin disease : implications for the development of severe reactive onchodermatitis (ROD)
- 2007
-
Ingår i: American Journal of Tropical Medicine and Hygiene. - Lawrence, Kans. : American society of tropical medicine and hygiene. - 0002-9637 .- 1476-1645. ; 77:6, s. 1074-8
-
Tidskriftsartikel (refereegranskat)abstract
- The pathologic manifestations of Onchocerca volvulus infection depend on the interplay between the host and the parasite. A genetic single nucleotide polymorphism in the Fc gamma RIIa gene, resulting in arginine (R) or histidine (H) at position 131, affects the binding to the different IgG subclasses and may influence the clinical variations seen in onchocerciasis. This study investigated the relationship between this polymorphism and disease outcome. Fc gamma RIIa genotyping was performed on clinically characterized onchocerciasis patients (N = 100) and healthy controls (N = 74). Fc gamma RIIa genotype R/R131 frequencies were significantly higher among patients with severe dermatopathology (P < 0.001). Increased risk of developing this form was mostly associated with one tribe (Masalit) (OR = 3.2, 95% CI 1-9.9, P = 0.042). The H131 allele was found to be significantly associated with a reduced risk of having the severe form of the disease (adjusted OR = 0.26, 95% CI = 0.13-0.46, P < 0.001). Our findings suggest that the polymorphism influences the clinical outcome of onchocerciasis.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Kaderi, Mohd Arifin, et al.
(författare)
-
LPL is the strongest prognostic factor in a comparative analysis of RNA-based markers in early chronic lymphocytic leukemia
- 2011
-
Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 96:8, s. 1153-1160
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:The expression levels of LPL, ZAP70, TCL1A, CLLU1 and MCL1 have recently been proposed as prognostic factors in chronic lymphocytic leukemia. However, few studies have systematically compared these different RNA-based markers.DESIGN AND METHODS:Using real-time quantitative PCR, we measured the mRNA expression levels of these genes in unsorted samples from 252 newly diagnosed chronic lymphocytic leukemia patients and correlated our data with established prognostic markers (for example Binet stage, CD38, IGHV gene mutational status and genomic aberrations) and clinical outcome.RESULTS:High expression levels of all RNA-based markers, except MCL1, predicted shorter overall survival and time to treatment, with LPL being the most significant. In multivariate analysis including the RNA-based markers, LPL expression was the only independent prognostic marker for overall survival and time to treatment. When studying LPL expression and the established markers, LPL expression retained its independent prognostic strength for overall survival. All of the RNA-based markers, albeit with varying ability, added prognostic information to established markers, with LPL expression giving the most significant results. Notably, high LPL expression predicted a worse outcome in good-prognosis subgroups, such as patients with mutated IGHV genes, Binet stage A, CD38 negativity or favorable cytogenetics. In particular, the combination of LPL expression and CD38 could further stratify Binet stage A patients.CONCLUSIONS:LPL expression is the strongest RNA-based prognostic marker in chronic lymphocytic leukemia that could potentially be applied to predict outcome in the clinical setting, particularly in the large group of patients with favorable prognosis.
|
|
| 9. |
- Labayen, Idoia, et al.
(författare)
-
Association of common variants of UCP2 gene with low-grade inflammation in Swedish children and adolescents : the European Youth Heart Study
- 2009
-
Ingår i: Pediatric Research. - : Nature Publishing Group. - 0031-3998 .- 1530-0447. ; 66:3, s. 350-354
-
Tidskriftsartikel (refereegranskat)abstract
- We examined the associations of two functional variants 866G>A and DEL/INS polymorphisms of UCP2 gene with low-grade inflammatory proteins (C-reactive protein, fibrinogen, complement C3 [C3], and complement C4 [C4]) in 131 children (52.7% boys, aged 9.5 +/- 0.4 y) and 118 adolescents (44.1% males, aged 15.5 +/- 0.4 y) selected from the European Youth Heart Study. Differences in inflammatory markers among the genotype variants of the two UCP2 gene polymorphisms were analyzed after adjusting for sex, age, pubertal stage, fitness, and fatness. The results showed that fibrinogen, C3, and C4 were higher in GG carriers than in subjects carrying the A allele of the 866G>A polymorphism of the UCP2 gene (UCP2 -866G>A) polymorphism (all p < 0.05). The DEL/DEL genotype of 45nt deletion/insertion variant polymorphism of the UCP2 gene (UCP2 DEL/INS) was associated with higher C3 (p < 0.05) than DEL/INS and INS/INS genotypes. This study provides evidence of a role of UCP2 -866G>A in modifying low-grade inflammatory state in apparently healthy children and adolescents. Given the implication of complement factors on atherosclerosis process, these results contribute to explain the reduced cardiovascular risk associated with the A allele of the UCP2 -866G>A polymorphism.
|
|
| 10. |
- Rostami, Elham, 1979-, et al.
(författare)
-
BDNF polymorphism predicts general intelligence after penetrating traumatic brain injury
- 2011
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:11, s. e27389-
-
Tidskriftsartikel (refereegranskat)abstract
- Neuronal plasticity is a fundamental factor in cognitive outcome following traumatic brain injury. Brain-derivedneurotrophic factor (BDNF), a member of the neurotrophin family, plays an important role in this process. While thereare many ways to measure cognitive outcome, general cognitive intelligence is a strong predictor of everyday decisionmaking,occupational attainment, social mobility and job performance. Thus it is an excellent measure of cognitive outcomefollowing traumatic brain injury (TBI). Although the importance of the single-nucleotide polymorphisms polymorphism oncognitive function has been previously addressed, its role in recovery of general intelligence following TBI is unknown. Wegenotyped male Caucasian Vietnam combat veterans with focal penetrating TBI (pTBI) (n = 109) and non-head injuredcontrols (n = 38) for 7 BDNF single-nucleotide polymorphisms. Subjects were administrated the Armed Forces QualificationTest (AFQT) at three different time periods: pre-injury on induction into the military, Phase II (10–15 years post-injury, andPhase III (30–35 years post-injury). Two single-nucleotide polymorphisms, rs7124442 and rs1519480, were significantlyassociated with post-injury recovery of general cognitive intelligence with the most pronounced effect at the Phase II timepoint, indicating lesion-induced plasticity. The genotypes accounted for 5% of the variance of the AFQT scores,independently of other significant predictors such as pre-injury intelligence and percentage of brain volume loss. Thesedata indicate that genetic variations in BDNF play a significant role in lesion-induced recovery following pTBI. Identifying theunderlying mechanism of this brain-derived neurotrophic factor effect could provide insight into an important aspect ofpost-traumatic cognitive recovery.
|
|
