| 1. |
- Shrine, N, et al.
(författare)
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Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk
- 2023
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 55:3, s. 410-
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Tidskriftsartikel (refereegranskat)abstract
- Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies.
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| 2. |
- Gordin, D., et al.
(författare)
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The effects of baroreflex activation therapy on blood pressure and sympathetic function in patients with refractory hypertension: the rationale and design of the Nordic BAT study
- 2017
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Ingår i: Blood Pressure. - : Informa UK Limited. - 0803-7051 .- 1651-1999. ; 26:5, s. 294-302
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To explore the effects of baroreflex activation therapy (BAT) on hypertension in patients with treatment resistant or refractory hypertension.Methods: This investigator-initiated randomized, double-blind, 1:1 parallel-design clinical trial will include 100 patients with refractory hypertension from 6 tertiary referral hypertension centers in the Nordic countries. A Barostim Neo System will be implanted and after 1 month patients will be randomized to either BAT for 16 months or continuous pharmacotherapy (BAT off) for 8 months followed by BAT for 8 months. A second randomization will take place after 16 months to BAT or BAT off for 3 months. Eligible patients have a daytime systolic ambulatory blood pressure (ABPM) of 145mm Hg, and/or a daytime diastolic ABPM of 95mm Hg after witnessed drug intake (including 3 antihypertensive drugs, preferably including a diuretic).Results: The primary end point is the reduction in 24-hour systolic ABPM by BAT at 8 months, as compared to pharmacotherapy. Secondary and tertiary endpoints are effects of BAT on home and office blood pressures, measures of indices of cardiac and vascular structure and function during follow-up, and safety.Conclusions: This academic initiative will increase the understanding of mechanisms and role of BAT in the refractory hypertension.
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| 3. |
- Ellaithi, M, et al.
(författare)
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A del(X)(p11) carrying SRY sequences in an infant with ambiguous genitalia
- 2006
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Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 6:11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: SRY (sex-determining region, Y) is the gene responsible of gonadal differentiation in the male and it is essential for the regular development of male genitalia. Translocations involving the human sex chromosomes are rarely reported, however here we are reporting a very rare translocation of SRY gene to the q -arm of a deleted X chromosome. This finding was confirmed by cytogenetic, fluorescent in situ hybridization (FISH) and polymerase chain reaction (PCR). CASE PRESENTATION: A 7-month infant was clinically diagnosed as an intersex case, with a phallus, labia majora and minora, a blind vagina and a male urethra. Neither uterus nor testes was detected by Ultrasonography. G-banding of his chromosomes showed 46,X,del(X)(p11) and fluorescent in situ hybridization (FISH) analysis showed a very small piece from the Y chromosome translocated to the q-arm of the del(X). Polymerase chain reaction (PCR) analysis revealed the presence of material from the sex-determining region Y (SRY) gene. CONCLUSION: It is suggested that the phenotype of the patient was caused by activation of the deleted X chromosome with SRY translocation, which is responsible for gonadal differentiation.
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| 4. |
- Rönnberg, AnnKristin, 1967-, et al.
(författare)
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Intervention during pregnancy to reduce excessive gestational weight gain : a randomised controlled trial
- 2015
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Ingår i: British Journal of Obstetrics and Gynecology. - : Wiley. - 1470-0328 .- 1471-0528. ; 122:4, s. 537-544
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate if a feasible, low-cost intervention could decrease the percentage of women gaining weight above the Institute of Medicine (IOM) recommendations on gestational weight gain (GWG) compared with standard maternity care.Design: A randomised controlled interventional design.Setting: Antenatal clinics (n=14) in orebro county, Sweden, participated.Population: Healthy women with a body mass index (BMI) 19kg/m(2), age 18years and adequate knowledge of Swedish language who signed in for maternity care at 16weeks of gestation.Methods: Standard care was compared with a composite intervention consisting of education on recommended GWG according to IOM, application of personalised weight graph, formalised prescription of exercise and regular monitoring of GWG at every antenatal visit.Outcome: The proportion of women gaining weight above IOM guidelines (1990) and mean GWG (kg) was compared between groups.Results: In all, 445 women were randomised and 374 women remained for analysis after delivery. A majority of the women analysed were normal weight (72%). The intervention reduced the proportion of women who exceeded the IOM guidelines (41.1% versus 50.0%). The reduction was, however, not statistically significant (P=0.086). Mean GWG was significantly lower among women receiving the intervention, 14.2kg (SD 4.4) versus 15.3kg (SD 5.4) in the standard care group (P=0.029).Conclusions: The low-cost intervention programme tested did significantly reduce the mean GWG but the proportion of women who exceeded the IOM recommendations for GWG was not significantly lower. ClinicalTrials.gov Id NCT00451425
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