Biomedical subjects

Valgerdur Steinthorsdottir

Publications and source records attributed to Valgerdur Steinthorsdottir.

7 recordsLinked to original sources

PubMed2006

Recurrence of hypertensive disorder in second pregnancy.

OBJECTIVE: The purpose of this study was to investigate the recurrence of hypertensive disorders in pregnancy with regard to the type of disorder, the onset of hypertension, and the modulating effect of overweight and weight gain between pregnancies. STUDY DESIGN: Maternity records from 896 parous women with hypertensive disorders in pregnancy in the first pregnancy were reviewed to reclassify disease status and calculate odds ratios for recurrence. RESULTS: Recurrence of hypertensive disorders in pregnancy occurred in 58% to 94% of second pregnancies, depending on first pregnancy disorder. Overweight (odds ratio, 1.82) and weight gain (odds ratio, 2.20) were related to recurrence among women with gestational hypertension. Early hypertension (<or =34 weeks of gestation) increased the recurrence risk for women with gestational hypertension (odds ratio, 1.85) and preeclampsia (odds ratio, 3.42). CONCLUSION: Recurrence of hypertensive disorders in pregnancy is common, but not specified by type of disorder in first pregnancy. Overweight and weight gain between pregnancies are associated with recurrent hypertensive disorders in pregnancy in women with gestational hypertension. Early onset of hypertension is a risk factor, independent of body weight.

Female↗

PubMed2005

A common inversion under selection in Europeans.

A refined physical map of chromosome 17q21.31 uncovered a 900-kb inversion polymorphism. Chromosomes with the inverted segment in different orientations represent two distinct lineages, H1 and H2, that have diverged for as much as 3 million years and show no evidence of having recombined. The H2 lineage is rare in Africans, almost absent in East Asians but found at a frequency of 20% in Europeans, in whom the haplotype structure is indicative of a history of positive selection. Here we show that the H2 lineage is undergoing positive selection in the Icelandic population, such that carrier females have more children and have higher recombination rates than noncarriers.

Chromosome Inversion↗

PubMed2004

Multiple novel transcription initiation sites for NRG1.

The large neuregulin 1 gene (NRG1) has been mapped to a 1.125 Mb region on chromosome 8p11-21. Three major forms of NRG1 (types I-III), all with distinct amino-termini encoded by unique 5'-exons, have been described. We report here the discovery of nine novel NRG1 exons, including six alternative 5'-exons, increasing the number of potential promoters in NRG1 from three to nine. The novel transcripts of NRG1 described here use the novel 5'-exons which are either coding or non-coding. The functional relevance of the predicted proteins they encode has not been evaluated. Three of the novel 5'-exons are well conserved in syntenic rat and mouse sequences; they encode proteins with novel amino-termini, here termed types IV-VI. NRG1 plays a central role in neural development and is most likely involved in regulation of synaptic plasticity, or how the brain responds or adapts to the environment. The unusually complex gene structure may facilitate spatial and temporal regulation of NRG1 expression, fine-tune NRG1 protein function at different stages during development of the nervous system, and adapt responses to the environment in the adult brain.

5' Flanking Region↗

PubMed2004

Neuregulin 1 and schizophrenia.

We discuss in this review the role of the neuregulin (NRG1) gene in schizophrenia. NRG1 contributes to the genetics of schizophrenia in both Icelandic and Scottish schizophrenia patients. NRG1 participates in glutamatergic signaling by regulating the N-methyl-D-aspartate (NMDA) receptor through the interaction of the NRG1 protein and its receptors. NRG1 plays a central role in neural development and is most likely involved in regulating synaptic plasticity, or how the brain responds or adapts to the environment. The discovery that defects in NRG1 signaling may be involved in some cases of schizophrenia, not only implicates NRG1, but suggests that its biological pathway, active both at developing and mature synapses, is worth inspecting further in a search for other schizophrenia genes possibly in epistasis with NRG1.

Animals↗

PubMed2004

Paternity change and the recurrence risk in familial hypertensive disorder in pregnancy.

OBJECTIVE: To investigate if there is an increased risk for recurrence of hypertensive disorder in pregnancy with a new partner and whether this is affected by maternal age and the interbirth interval through use of familial material. METHODS: Data on 614 multiparous women, with confirmed de novo hypertensive disorder in a first pregnancy, were used to assess the effect of paternity and interbirth interval on recurrence of hypertensive disorders. RESULTS: There were 121 women (19.7%) who had changed partner. Recurrent hypertension occurred in 318 women (64.5%) with the same partner and in 75 women (62%) with a new partner. The odds ratio (OR) for recurrence with the same partner was 1.115 (95% CI 0.739-1.680) and with a new partner 0.897 (95% CI 0.595-1.353). The mean interbirth interval was longer for women with recurrent hypertension (4.9 vs. 4.0 years, p = 0.0002). The OR for developing recurrent hypertensive disorder was 1.154 (95% CI 1.049-1.269) for every interval year with the same partner and 1.145 (95% CI 0.958-1.368) with a new partner after correction for maternal age. CONCLUSION: In women with a positive family history and previous hypertension in pregnancy, change of paternity does not influence the risk of recurrence. Increasing interbirth interval may account for a 15% recurrence risk for each year, independent of maternal age. There was no indication that a change of partner conferred any influence on the recurrence risk that is not explained with birth interval or age.

Female↗

PubMed2002

Association of neuregulin 1 with schizophrenia confirmed in a Scottish population.

Recently, we identified neuregulin 1 (NRG1) as a susceptibility gene for schizophrenia in the Icelandic population, by a combined linkage and association approach. Here, we report the first study evaluating the relevance of NRG1 to schizophrenia in a population outside Iceland. Markers representing a core at-risk haplotype found in Icelanders at the 5' end of the NRG1 gene were genotyped in 609 unrelated Scottish patients and 618 unrelated Scottish control individuals. This haplotype consisted of five SNP markers and two microsatellites, which all appear to be in strong linkage disequilibrium. For the Scottish patients and control subjects, haplotype frequencies were estimated by maximum likelihood, using the expectation-maximization algorithm. The frequency of the seven-marker haplotype among the Scottish patients was significantly greater than that among the control subjects (10.2% vs. 5.9%, P=.00031). The estimated risk ratio was 1.8, which is in keeping with our report of unrelated Icelandic patients (2.1). Three of the seven markers in the haplotype gave single-point P values ranging from .000064 to .0021 for the allele contributing to the at-risk haplotype. This direct replication of haplotype association in a second population further implicates NRG1 as a factor that contributes to the etiology of schizophrenia.

Algorithms↗

PubMed2002

Neuregulin 1 and susceptibility to schizophrenia.

The cause of schizophrenia is unknown, but it has a significant genetic component. Pharmacologic studies, studies of gene expression in man, and studies of mouse mutants suggest involvement of glutamate and dopamine neurotransmitter systems. However, so far, strong association has not been found between schizophrenia and variants of the genes encoding components of these systems. Here, we report the results of a genomewide scan of schizophrenia families in Iceland; these results support previous work, done in five populations, showing that schizophrenia maps to chromosome 8p. Extensive fine-mapping of the 8p locus and haplotype-association analysis, supplemented by a transmission/disequilibrium test, identifies neuregulin 1 (NRG1) as a candidate gene for schizophrenia. NRG1 is expressed at central nervous system synapses and has a clear role in the expression and activation of neurotransmitter receptors, including glutamate receptors. Mutant mice heterozygous for either NRG1 or its receptor, ErbB4, show a behavioral phenotype that overlaps with mouse models for schizophrenia. Furthermore, NRG1 hypomorphs have fewer functional NMDA receptors than wild-type mice. We also demonstrate that the behavioral phenotypes of the NRG1 hypomorphs are partially reversible with clozapine, an atypical antipsychotic drug used to treat schizophrenia.

Animals↗