1.
Blennow, Kaj, 1958, et al.
(författare)
No association between the alpha2-macroglobulin (A2M) deletion and Alzheimer's disease, and no change in A2M mRNA, protein, or protein expression.
2000
Ingår i: Journal of neural transmission (Vienna, Austria : 1996). - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 107:8-9, s. 1065-79
Tidskriftsartikel (refereegranskat) abstract
A polymorphism consisting of a deletion near the 5' splice site of exon 18 on the alpha2-macroglobulin (A2M) gene (A2M-2) has been suggested to be associated with Alzheimer's disease (AD) in family-based studies. We studied the A2M-2 allele together with the ApoE alleles in a large series on patients with AD (n = 449) and age-matched controls (n = 349). Neuropathologically confirmed diagnoses were available in 199 cases (94 AD and 107 control cases). We found no increase in A2M-2 genotype or allele frequencies in AD (27.5% and 14.6%) versus controls (26.4% and 14.9%). In contrast, a marked increase (p < 0.0001) in ApoE epsilon4 genotype or allele frequencies was found in AD (66.6% and 41.2%) as compared with controls (29.8% and 16.5%), suggesting sufficient statistical power in our sample. No relation was found between the A2M-2 and the ApoE epsilon4 allele. No change in A2M exon 17-18 mRNA size or sequence or A2M protein size was found in cases carrying the A2M-2 deletion, suggesting that there is no biological consequences of the A2M intronic deletion. No change in A2M protein level in cerebrospinal fluid was found in AD, suggesting that the A2M-2 allele does not effect the A2M protein expression in the brain. The lack of an association between the A2M-2 allele and AD in the present study, and the lack of abnormalities in the A2M mRNA or protein suggest that the A2M-2 allele is not associated with AD.
2.
Johansson, Peter, 1958, et al.
(författare)
Increased risk for vascular complications in PRV-1 positive patients with essential thrombocythaemia.
2003
Ingår i: British journal of haematology. - 0007-1048. ; 123:3, s. 513-6
Tidskriftsartikel (refereegranskat) abstract
Essential thrombocythaemia (ET) is a heterogeneous disorder with respect to plasma erythropoietin concentration at diagnosis and clonality of haematopoiesis. Polycythaemia rubra vera-1 (PRV-1) positivity, i.e. PRV-1 mRNA overexpression, is known to be present in the vast majority of patients with polycythaemia vera and also in some patients with ET. In the present study, PRV-1 expression was quantified by real-time polymerase chain reaction in 70 ET patients; 17 of them (24%) were found to be PRV-1 positive. Ten of the 17 PRV-1 positive ET patients had experienced thromboembolic complications compared with 14 of 53 PRV-1 negative patients, the difference between the two groups being statistically significant (P=0.02). In addition, the frequency of total vascular complications, thromboembolic events and major bleedings, was significantly higher in the group of PRV-1 positive as compared with PRV-1 negative ET patients (P=0.03). The time from diagnosis of ET to the requirement of platelet-lowering therapy was significantly shorter in PRV-1 positive compared with PRV-1 negative ET patients (P=0.014). It can be concluded that PRV-1 positive patients appear to suffer from a more aggressive disorder with increased risk for vascular complications and a greater need for platelet-lowering therapy, compared with PRV-1 negative ET patients.
3.
Johansson, Peter, 1958, et al.
(författare)
The presence of a significant association between elevated PRV-1 mRNA expression and low plasma erythropoietin concentration in essential thrombocythaemia.
2003
Ingår i: European journal of haematology. - 0902-4441. ; 70:6, s. 358-62
Tidskriftsartikel (refereegranskat) abstract
Approximately 45% of newly diagnosed patients with essential thrombocythaemia (ET) demonstrate subnormal plasma erythropoietin (EPO) concentrations, which constitutes a risk factor for occlusive vascular events. In 58 ET patients, a possible association between polycythaemia rubra vera-1 (PRV-1) overexpression and subnormal plasma EPO was investigated, which was always measured prior to the institution of platelet lowering agents. At the time when PRV-1 expression was measured, 28 of 58 (48%) ET patients had received platelet lowering treatment. PRV-1 expression was measured by quantitative real-time reverse transcription-polymerase chain reaction assay of mRNA extracted from purified peripheral blood buffy coat. The cycle threshold (CT) value of PRV-1 was determined and was divided with the CT value for the housekeeping GAPDH gene transcript. A quotient <0.93 was defined as PRV-1 positive. Of the ET patients 12 of 58 (21%) were PRV-1 positive and 19 of 58 (33%) demonstrated subnormal plasma EPO. In the 58 ET patients there was a significant association between low plasma EPO and PRV-1 positive results (P = 0.001). The 30 ET patients who had not received any platelet lowering treatment showed a significant (P = 0.005) relation between PRV-1 positivity and subnormal plasma EPO. No such relationship was present in the 28 ET patients who had received prior treatment with the above drugs (P = 0.147).
4.
Campagnoli, Monica, et al.
(författare)
A novel splicing mutation causes an undescribed type of analbuminemia.
2002
Ingår i: Biochimica et biophysica acta. - 0006-3002. ; 1586:1, s. 43-9
Tidskriftsartikel (refereegranskat) abstract
Analbuminemia is a rare autosomal recessive disorder manifested by the absence or severe reduction of circulating serum albumin in homozygous subjects. In this report we describe a new molecular defect that caused the analbuminemic trait in a newborn of Iraqi origin. When the parents' DNA was analyzed, both subjects were found to be heterozygous for the same mutation found in the infant. All the 14 exon and flanking intron sequences of the albumin gene were amplified via PCR and screened for mutations by SSCP and heteroduplex analysis. A mutation in the DNA region encoding exon 1 and its flanking intron was revealed by the presence of a heteroduplex. The fragment, which was directly DNA sequenced, contains a previously unreported single nucleotide change, consisting in a G to A substitution at nucleotide 118 in the structural gene of the human protein. This mutation, involving the first base of intron 1, destroys the GT dinucleotide consensus sequence found at the 5' end of most intervening sequences and causes the defective pre-mRNA splicing responsible for the analbuminemic trait.
5.
Zetterberg, Henrik, 1973, et al.
(författare)
Increased frequency of combined methylenetetrahydrofolate reductase C677T and A1298C mutated alleles in spontaneously aborted embryos.
2002
Ingår i: European journal of human genetics : EJHG. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 10:2, s. 113-8
Tidskriftsartikel (refereegranskat) abstract
The pathogenesis of spontaneous abortion is complex, presumably involving the interaction of several genetic and environmental factors. The methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphisms are commonly associated with defects in folate dependent homocysteine metabolism and have been implicated as risk factors for recurrent embryo loss in early pregnancy. In the present study we have determined the prevalence of combined MTHFR C677T and A1298C polymorphisms in DNA samples from spontaneously aborted embryos (foetal death between sixth and twentieth week after conception) and adult controls using solid-phase minisequencing technique. There was a significant odds ratio of 14.2 (95% CI 1.78-113) in spontaneously aborted embryos comparing the prevalence of one or more 677T and 1298C alleles vs the wild type combined genotype (677CC/1298AA), indicating that the MTHFR polymorphisms may have a major impact on foetal survival. Combined 677CT/1298CC, 677TT/1298AC or 677TT/1298CC genotypes, which contain three or four mutant alleles, were not detected in any of the groups, suggesting complete linkage disequilibrium between the two polymorphisms. The present finding of high prevalence of mutated MTHFR genotypes in spontaneously aborted embryos emphasises the potential protective role of periconceptional folic acid supplementation.
6.
Zetterberg, Henrik, 1973, et al.
(författare)
Influence of the apolipoprotein E epsilon4 allele on human embryonic development.
2002
Ingår i: Neuroscience letters. - 0304-3940. ; 324:3, s. 189-92
Tidskriftsartikel (refereegranskat) abstract
Human apolipoprotein E (apoE) exists in three major isoforms encoded by distinct alleles (APOE epsilon2, epsilon3 and epsilon4) and has important functions in nerve development and repair. Inheritance of the 4 allele is a major risk factor for the development of Alzheimer's disease. To investigate the role of APOE polymorphisms in embryonic development, we analyzed the APOE genotypes of 81 spontaneously aborted embryos and 110 adult controls using a solid-phase minisequencing technique. The epsilon4 allele was significantly less frequent in the spontaneous abortion group than in the control group (P=0.009), while the frequency of epsilon3 was significantly increased (P=0.005), suggesting that epsilon4 may have protective effects during embryogenesis. These protective effects might counterbalance the deleterious age-related effects of the epsilon4 allele in natural selection.
