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Johansson, Gunnar
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Ellingsen, J., Johansson, G., Larsson, K., Lisspers, K., Malinovschi, A., Ställberg, B., . . . Jansson, C. (2020). Impact of Comorbidities and Commonly Used Drugs on Mortality in COPD - Real-World Data from a Primary Care Setting. The International Journal of Chronic Obstructive Pulmonary Disease, 15, 235-245
Åpne denne publikasjonen i ny fane eller vindu >>Impact of Comorbidities and Commonly Used Drugs on Mortality in COPD - Real-World Data from a Primary Care Setting
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2020 (engelsk)Inngår i: The International Journal of Chronic Obstructive Pulmonary Disease, ISSN 1176-9106, E-ISSN 1178-2005, Vol. 15, s. 235-245Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Background: Life expectancy is significantly shorter for patients with chronic obstructive pulmonary disease (COPD) than the general population. Concurrent diseases are known to infer an increased mortality risk in those with COPD, but the effects of pharmacological treatments on survival are less established. This study aimed to examine any associations between commonly used drugs, comorbidities and mortality in Swedish real-world primary care COPD patients.

Methods: Patients with physician-diagnosed COPD from a large primary care population were observed retrospectively, utilizing primary care records and mandatory Swedish national registers. The time to all-cause death was assessed in a stepwise multiple Cox proportional hazards regression model including demography, socioeconomic factors, exacerbations, comorbidities and medication.

Results: During the observation period (1999-2009) 5776 (32.5%) of 17,745 included COPD patients died. Heart failure (hazard ratio [HR]: 1.88, 95% confidence interval [CI]: 1.74-2.04), stroke (HR: 1.52, 95% CI: 1.40-1.64) and myocardial infarction (HR: 1.40, 95% CI: 1.24-1.58) were associated with an increased risk of death. Use of inhaled corticosteroids (ICS; HR: 0.79, 95% CI: 0.66-0.94), beta-blockers (HR: 0.86, 95% CI: 0.76-0.97) and acetylsalicylic acid (ASA; HR: 0.87, 95% CI: 0.77-0.98) was dose-dependently associated with a decreased risk of death, whereas use of long-acting muscarinic antagonists (LAMA; HR: 1.33, 95% CI: 1.14-1.55) and N-acetylcysteine (NAC; HR: 1.26, 95% CI: 1.08-1.48) were dose-dependently associated with an increased risk of death in COPD patients.

Conclusion: This large, retrospective, observational study of Swedish real-world primary care COPD patients indicates that coexisting heart failure, stroke and myocardial infarction were the strongest predictors of death, underscoring the importance of timely recognition and treatment of comorbidities. A decreased risk of death associated with the use of ICS, beta-blockers and ASA, and an increased risk associated with the use of LAMA and NAC, was also found.

sted, utgiver, år, opplag, sider
DOVE MEDICAL PRESS LTD, 2020
Emneord
observational, LAMA, inhaled corticosteroids, beta-blockers, acetylsalicylic acid, chronic obstructive pulmonary disease
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-407514 (URN)10.2147/COPD.S231296 (DOI)000515171300001 ()32099348 (PubMedID)
Forskningsfinansiär
AstraZeneca
Tilgjengelig fra: 2020-03-25 Laget: 2020-03-25 Sist oppdatert: 2020-03-25bibliografisk kontrollert
Lisspers, K., Larsson, K., Janson, C., Ställberg, B., Tsiligianni, I., Gutzwiller, F. S., . . . Johansson, G. (2019). Gender differences among Swedish COPD patients: results from the ARCTIC, a real-world retrospective cohort study. npj Primary Care Respiratory Medicine, 29, Article ID 45.
Åpne denne publikasjonen i ny fane eller vindu >>Gender differences among Swedish COPD patients: results from the ARCTIC, a real-world retrospective cohort study
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2019 (engelsk)Inngår i: npj Primary Care Respiratory Medicine, E-ISSN 2055-1010, Vol. 29, artikkel-id 45Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

The present study aimed to generate real-world evidence regarding gender differences among chronic obstructive pulmonary disease (COPD) patients, especially as regards the diagnosis and outcomes in order to identify areas for improvement and management and optimize the associated healthcare resource allocation. ARCTIC is a large, real-world, retrospective cohort study conducted in Swedish COPD patients and a matched reference population from 52 primary care centers in 2000-2014. The incidence of COPD, prevalence of asthma and other comorbidities, risk of exacerbations, mortality rate, COPD drug prescriptions, and healthcare resource utilization were analyzed. In total, 17,479 patients with COPD were included in the study. During the study period, COPD was more frequent among women (53.8%) and women with COPD experienced more exacerbations vs. men (6.66 vs. 4.66). However, the overall mortality rate was higher in men compared with women (45% vs. 38%), but no difference for mortality due to COPD was seen between genders over the study period. Women seemed to have a greater susceptibility to asthma, fractures, osteoporosis, rheumatoid arthritis, rhinitis, depression, and anxiety, but appeared less likely to have diabetes, kidney diseases, and cardiovascular diseases. Furthermore, women had a greater risk of COPD-related hospitalization and were likely to receive a significantly higher number of COPD drug prescriptions compared with men. These results support the need to reduce disease burden among women with COPD and highlight the role of healthcare professionals in primary care who should consider all these parameters in order to properly diagnose and treat women with COPD.

HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-400331 (URN)10.1038/s41533-019-0157-3 (DOI)000502995600001 ()31822681 (PubMedID)
Tilgjengelig fra: 2019-12-19 Laget: 2019-12-19 Sist oppdatert: 2020-02-25bibliografisk kontrollert
Larsson, K., Janson, C., Ställberg, B., Lisspers, K., Olsson, P., Kostikas, K., . . . Johansson, G. (2019). Impact of COPD diagnosis timing on clinical and economic outcomes: the ARCTIC observational cohort study. The International Journal of Chronic Obstructive Pulmonary Disease, 14, 995-1008
Åpne denne publikasjonen i ny fane eller vindu >>Impact of COPD diagnosis timing on clinical and economic outcomes: the ARCTIC observational cohort study
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2019 (engelsk)Inngår i: The International Journal of Chronic Obstructive Pulmonary Disease, ISSN 1176-9106, E-ISSN 1178-2005, Vol. 14, s. 995-1008Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Purpose: Assess the clinical and economic consequences associated with an early versus late diagnosis in patients with COPD.

Patients and methods: In a retrospective, observational cohort study, electronic medical record data (2000-2014) were collected from Swedish primary care patients with COPD. COPD indicators (pneumonia, other respiratory diseases, oral corticosteroids, antibiotics for respiratory infections, prescribed drugs for respiratory symptoms, lung function measurement) registered prior to diagnosis were applied to categorize patients into those receiving early (2 or less indicators) or late diagnosis (3 or more indicators registered >90 days preceding a COPD diagnosis). Outcome measures included annual rate of and time to first exacerbation, mortality risk, prevalence of comorbidities and health care utilization.

Results: More patients with late diagnosis (n=8827) than with early diagnosis (n=3870) had a recent comorbid diagnosis of asthma (22.0% vs 3.9%; P<0.0001). Compared with early diagnosis, patients with late diagnosis had a higher exacerbation rate (hazard ratio [HR] 1.89, 95% confidence interval [CI]: 1.83-1.96; P<0.0001) and shorter time to first exacerbation (HR 1.61, 95% CI: 1.54-1.69; P<0.0001). Mortality was not different between groups overall but higher for late versus early diagnosis, after excluding patients with past asthma diagnosis (HR 1.10, 95% CI: 1.02-1.18; P=0.0095). Late diagnosis was also associated with higher direct costs than early diagnosis.

Conclusion: Late COPD diagnosis is associated with higher exacerbation rate and increased comorbidities and costs compared with early diagnosis. The study highlights the need for accurate diagnosis of COPD in primary care in order to reduce exacerbations and the economic burden of COPD.

Emneord
chronic obstructive pulmonary disease, diagnosis, Sweden, exacerbations, mortality
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-384473 (URN)10.2147/COPD.S195382 (DOI)000468106900001 ()
Tilgjengelig fra: 2019-06-11 Laget: 2019-06-11 Sist oppdatert: 2019-06-11bibliografisk kontrollert
Jansson, C., Benhaddi, H., Törnblom, M., Uhde, M. & Johansson, G. (2019). Real-world evidence effect of budesonide+formoterol Spiromax on patients with asthma and chronic obstructive pulmonary disease in Sweden. European Clinical Respiratory Journal, 6(1), Article ID 1660565.
Åpne denne publikasjonen i ny fane eller vindu >>Real-world evidence effect of budesonide+formoterol Spiromax on patients with asthma and chronic obstructive pulmonary disease in Sweden
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2019 (engelsk)Inngår i: European Clinical Respiratory Journal, ISSN 2001-8525, Vol. 6, nr 1, artikkel-id 1660565Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Background and Objective: Despite improved asthma and chronic obstructive pulmonary disease (COPD) management, treatment remains inadequate in many patients. Understanding the impact of current treatment in settings outside of controlled trials would add important clinical decision-making information. This study evaluated costs and outcomes associated with budesonide+formoterol (BF) Spiromax® initiation among real-world Swedish patients with asthma and/or COPD.

Methods:In this retrospective observational analysis of Swedish patients with asthma and/or COPD, data were collected from the National Patient Register, National Dispensed Drug Register, and Cause of Death Register 1 year before and after initiating BF Spiromax (index date). Outcomes included exacerbation occurrence, treatment patterns, inpatient care, and healthcare costs.

Results: The study included 576 patients (asthma: 51.6%; COPD: 32.8%; and asthma and COPD: 15.6%). Following BF Spiromax initiation in asthma patients, there were significant decreases in exacerbations (41.1% to 30.0%; P < 0.001), mean comorbidity-related inpatient visits (0.5 to 0.2; P < 0.001), and inpatient days (1.9 to 0.6; P = 0.006), and a trend toward fewer asthma-related inpatient visits (mean, 0.2 to 0.1; P = 0.056) and asthma-related inpatient days (mean, 0.7 to 0.3; P = 0.060). Increased inpatient utilization was observed in patients with COPD or both diagnoses. All-cause and asthma-/COPD-related medication costs decreased in all groups.

Conclusions: After switching to BF Spiromax, asthma patients had fewer exacerbations and hospital visits versus the prior year and COPD patients showed an increase in all-cause and COPD-related healthcare resource utilization. All-cause and asthma-/COPD-related medication costs decreased in all groups after switching to BF Spiromax.

Emneord
Asthma, chronic obstructive pulmonary disease, inhalation devices, Spiromax, real-world treatment outcomes
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-394983 (URN)10.1080/20018525.2019.1660565 (DOI)000486235200001 ()
Tilgjengelig fra: 2019-10-11 Laget: 2019-10-11 Sist oppdatert: 2019-10-11bibliografisk kontrollert
Björk, A., Ribom, E., Johansson, G., Scragg, R., Mellstrom, D., Grundberg, E., . . . Kindmark, A. (2019). Variations in the vitamin D receptor gene are not associated with measures of muscle strength, physical performance, or falls in elderly men: Data from MrOS Sweden. Journal of Steroid Biochemistry and Molecular Biology, 187, 160-165
Åpne denne publikasjonen i ny fane eller vindu >>Variations in the vitamin D receptor gene are not associated with measures of muscle strength, physical performance, or falls in elderly men: Data from MrOS Sweden
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2019 (engelsk)Inngår i: Journal of Steroid Biochemistry and Molecular Biology, ISSN 0960-0760, E-ISSN 1879-1220, Vol. 187, s. 160-165Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

The vitamin D receptor (VDR) has been proposed as a candidate gene for several musculoskeletal phenotypes. However, previous results on the associations between genetic variants of the VDR with muscle strength and falls have been contradictory. The MrOS Sweden survey, a prospective population-based cohort study of 3014 elderly men (mean age 75 years, range 69-81) offered the opportunity to further investigate these associations. At baseline, data were collected on muscle strength and also the prevalence of falls during the previous 12 months. Genetic association analysis was performed for 7 Single Nucleotide Polymorphisms (SNPs), covering the genetic region surrounding the VDR gene in 2924 men with available samples of DNA. Genetic variations in the VDR were not associated with five different measurements of muscle strength or physical performance (hand grip strength right and left, 6 m walking test (easy and narrow) and timed-stands test). However, one of the 7 SNPs of the gene for the VDR receptor, rs7136534, was associated with prevalence of falls (33.6% of the AA, 14.6% of the AG and 16.5% of the GG allele). In conclusion, VDR genetic variants are not related to muscle strength or physical performance in elderly Swedish men. The role of the rs7136534 SNP for the occurrence of falls is not clear.

Emneord
Vitamin D receptor gene, Polymorphisms, Muscle strength, Physical performance, Falls
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-379342 (URN)10.1016/j.jsbmb.2018.11.014 (DOI)000459952100021 ()30476589 (PubMedID)
Forskningsfinansiär
Swedish Research Council, 2016-01001Knut and Alice Wallenberg Foundation, KAW 2015.0317Torsten Söderbergs stiftelseNovo Nordisk
Tilgjengelig fra: 2019-03-15 Laget: 2019-03-15 Sist oppdatert: 2019-03-15bibliografisk kontrollert
Lisspers, K., Janson, C., Larsson, K., Johansson, G., Telg, G., Thuresson, M. & Ställberg, B. (2018). Comorbidity, disease burden and mortality across age groups in a Swedish primary care asthma population: An epidemiological register study (PACEHR). Respiratory Medicine, 136, 15-20
Åpne denne publikasjonen i ny fane eller vindu >>Comorbidity, disease burden and mortality across age groups in a Swedish primary care asthma population: An epidemiological register study (PACEHR)
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2018 (engelsk)Inngår i: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 136, s. 15-20Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Background:

Asthma is often associated with other diseases. To identify and manage comorbidities is important, as these conditions may increase the disease burden.

Objective:

To describe the prevalence of comorbidities, disease burden and mortality across age groups in a large Swedish primary care real-life asthma population.

Methods:

Observational cohort study of asthma patients, all ages, identified from electronic medical records by ICD-10-CM code, data from 36 primary care centers. Data were linked to national mandatory Swedish health registers. Comorbidities were identified by ICD-10-CM codes and collected from electronic medical records and the National Patient Registers, mortality data from the Cause of Death Register. Exacerbations were defined as hospitalizations due to asthma, and/or emergency visits at hospital and/or prescription claims of oral steroids.

Results:

In total 33,468 patients ( 58% women) were included. The most prevalent comorbidities were acute upper respiratory tract infection ( 53%), rhinitis ( 25%), acute lower respiratory tract infection ( 25%), hypertension ( 21%), anxiety and depression ( 20%). The comorbidities associated with highest risk for an exacerbation were COPD OR 1.98 ( 95% CI: 1.80-2.19), nasal polyps OR 1.75 ( 95% CI: 1.49-2.05) and rhinitis OR 1.52 ( 95% CI: 1.41-1.63). All-cause mortality was similar to the Swedish population, 1011 deaths per 100,000 person/year compared with 1058 deaths ( standardized risk=0.99 [ 95% CI: 0.95-1.04]). The pulmonary related death rate was greater in the study population versus the Swedish population ( 122 versus 72 per 100,000person/year).

Conclusion:

Comorbid disease was frequent in this large real-life asthma population with an impact on exacerbations. To identify and treat comorbidities with impact on asthma outcomes are essential to improve

Emneord
Asthma, Comorbidity, Mortality, Primary care, Observational
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-351269 (URN)10.1016/j.rmed.2018.01.020 (DOI)000426428800003 ()29501242 (PubMedID)
Forskningsfinansiär
AstraZeneca
Tilgjengelig fra: 2018-06-04 Laget: 2018-06-04 Sist oppdatert: 2018-06-04bibliografisk kontrollert
Lisspers, K., Larsson, K., Johansson, G., Janson, C., Costa-Scharplatz, M., Gruenberger, J.-B., . . . Ställberg, B. (2018). Economic burden of COPD in a Swedish cohort: the ARCTIC study. The International Journal of Chronic Obstructive Pulmonary Disease, 13, 275-285
Åpne denne publikasjonen i ny fane eller vindu >>Economic burden of COPD in a Swedish cohort: the ARCTIC study
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2018 (engelsk)Inngår i: The International Journal of Chronic Obstructive Pulmonary Disease, ISSN 1176-9106, E-ISSN 1178-2005, Vol. 13, s. 275-285Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Background: We assessed direct and indirect costs associated with COPD in Sweden and examined how these costs vary across time, age, and disease stage in a cohort of patients with COPD and matched controls in a real-world, primary care (PC) setting.

Patients and methods: Data from electronic medical records linked to the mandatory national health registers were collected for COPD patients and a matched reference population in 52 PC centers from 2000 to 2014. Direct health care costs (drug, outpatient or inpatient, PC, both COPD related and not COPD related) and indirect health care costs (loss of income, absenteeism, loss of productivity) were assessed.

Results: A total of 17,479 patients with COPD and 84,514 reference controls were analyzed. During 2013, direct costs were considerably higher among the COPD patient population ((sic)13,179) versus the reference population ((sic)2,716), largely due to hospital nights unrelated to COPD. Direct costs increased with increasing disease severity and increasing age and were driven by higher respiratory drug costs and non-COPD-related hospital nights. Indirect costs (similar to(sic)28,000 per patient) were the largest economic burden in COPD patients of working age during 2013.

Conclusion: As non-COPD-related hospital nights represent the largest direct cost, management of comorbidities in COPD would offer clinical benefits and relieve the financial burden of disease.

sted, utgiver, år, opplag, sider
DOVE MEDICAL PRESS LTD, 2018
Emneord
COPD, direct cost, indirect cost, burden, Sweden
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-341586 (URN)10.2147/COPD.S149633 (DOI)000422631500001 ()29391785 (PubMedID)
Tilgjengelig fra: 2018-02-12 Laget: 2018-02-12 Sist oppdatert: 2018-02-12bibliografisk kontrollert
Johansson, G., Mushnikov, V., Bäckström, T., Engström, A., Khalid, J. M., Wall, J. & Hoti, F. (2018). Exacerbations and healthcare resource utilization among COPD patients in a Swedish registry-based nation-wide study. BMC Pulmonary Medicine, 18, Article ID 17.
Åpne denne publikasjonen i ny fane eller vindu >>Exacerbations and healthcare resource utilization among COPD patients in a Swedish registry-based nation-wide study
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2018 (engelsk)Inngår i: BMC Pulmonary Medicine, ISSN 1471-2466, E-ISSN 1471-2466, Vol. 18, artikkel-id 17Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Background: Exacerbations of chronic obstructive pulmonary disease (COPD) are an important measure of disease severity in terms of impaired disease progression, increased recovery time, healthcare resource utilization, overall morbidity and mortality. We aimed to quantify exacerbation and healthcare resource utilization rates among COPD patients in Sweden with respect to baseline treatments, exacerbation history, and comorbidities.

Methods: Patients with a COPD or chronic bronchitis (CB) diagnosis in secondary care at age of >= 40 years on 1.7. 2009 were identified and followed until 1.7.2010 or death. Severe exacerbations were defined as hospitalizations due to respiratory disease, and healthcare resource utilization was measured by all-cause hospitalizations and secondary care visits. Poisson regression was used adjusting for age, gender, time since COPD/CB diagnosis, and Charlson comorbidity index.

Results: In 88,548 patients (54% females, mean age 72 years), previous respiratory hospitalizations and current high use of COPD medication (double or triple therapy) predicted an 8.3-fold increase in severe exacerbation rates and 1. 8-fold increase in healthcare resource utilization rates in the following year, compared to patients without combination treatment and/or history of severe exacerbations.

Conclusions: COPD/CB patients with history of severe exacerbations and high use of COPD medication experienced a significantly increased rate of severe exacerbations and healthcare resource utilization during the one-year follow-up.

sted, utgiver, år, opplag, sider
BIOMED CENTRAL LTD, 2018
Emneord
COPD, Healthcare resource utilization, Exacerbations, Hospitalizations, Burden of disease, Chronic bronchitis, Pharmacoepidemiology
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-346227 (URN)10.1186/s12890-018-0573-0 (DOI)000423718000003 ()29370846 (PubMedID)
Tilgjengelig fra: 2018-03-19 Laget: 2018-03-19 Sist oppdatert: 2018-03-19bibliografisk kontrollert
Sandelin, M., Mindus, S., Thuresson, M., Lisspers, K., Ställberg, B., Johansson, G., . . . Janson, C. (2018). Factors associated with lung cancer in COPD patients. The International Journal of Chronic Obstructive Pulmonary Disease, 13, 1833-1839
Åpne denne publikasjonen i ny fane eller vindu >>Factors associated with lung cancer in COPD patients
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2018 (engelsk)Inngår i: The International Journal of Chronic Obstructive Pulmonary Disease, ISSN 1176-9106, E-ISSN 1178-2005, Vol. 13, s. 1833-1839Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Background: The risk of dying of lung cancer is up to eightfold higher in patients with COPD than in age- and gender-matched controls. The aim of this study was to investigate the factors associated with lung cancer in a large cohort of COPD patients from primary care centers.

Methods: To analyze whether age, gender, socioeconomic factors, comorbidity, and medication affect the risk of lung cancer in COPD, we used a COPD cohort of primary care patients. Data from primary care medical records and mandatory Swedish national registers were collected and linked in this population-based, retrospective observational registry study (NCT01146392).

Results: Of the total cohort, 19,894 patients were included in the study. Five hundred and ninety-four lung cancer cases were diagnosed, corresponding to 3.0% of the studied population. In a multivariate analysis, the risk of lung cancer was lower if the COPD patients had a concurrent asthma diagnosis (HR: 0.54, CI: 0.41-0.71), while the risk of lung cancer increased with increasing age. A decreased lung cancer risk was observed in an exposure-dependent manner in patients who were prescribed inhaled corticosteroids (HR: 0.52, CI: 0.37-0.73), while the opposite was found for the use of acetylsalicylic acid (HR: 1.58, CI: 1.15-2.16).

Conclusion: In this large population-based cohort, a concurrent asthma diagnosis and use of inhaled corticosteroids were independently related to decreased risk of lung cancer in COPD patients, while the use of acetylsalicylic acid was associated with an increased risk. The findings of the present study should be seen as hypothesis generating and need to be confirmed in prospective studies.

sted, utgiver, år, opplag, sider
DOVE MEDICAL PRESS LTD, 2018
Emneord
asthma, NSCLC, risk factor, ACO, inhaled corticosteroids
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-357778 (URN)10.2147/COPD.S162484 (DOI)000434137100001 ()29922050 (PubMedID)
Forskningsfinansiär
AstraZeneca
Tilgjengelig fra: 2018-08-22 Laget: 2018-08-22 Sist oppdatert: 2018-08-22bibliografisk kontrollert
Björk, A., Mellström, D., Ohlsson, C., Karlsson, M., Mallmin, H., Johansson, G., . . . Kindmark, A. (2018). Haplotypes in the CYP2R1 gene are associated with levels of 25(OH)D and bone mineral density, but not with other markers of bone metabolism (MrOS Sweden). PLoS ONE, 13(12), Article ID e0209268.
Åpne denne publikasjonen i ny fane eller vindu >>Haplotypes in the CYP2R1 gene are associated with levels of 25(OH)D and bone mineral density, but not with other markers of bone metabolism (MrOS Sweden)
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2018 (engelsk)Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, nr 12, artikkel-id e0209268Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Objective: Polymorphisms in the CYP2R1 gene encoding Vitamin D 25-hydroxylase have been reported to correlate with circulating levels of 25-OH vitamin D3 (25(OH)D). It is unknown whether these variations also affect overall bone metabolism. In order to elucidate the overall associations of polymorphisms in the CYP2R1, we studied haplotype tagging single nucleotide polymorphisms (SNPs) in the gene and serum levels of 25(OH)D, calcium, phosphate, parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF23), as well as bone mineral density (BMD).

Methods: Baseline data on serum parameters and BMD from MrOS Sweden, a prospective population-based cohort study of elderly men (mean age 75 years, range 69-81), were analyzed. Genotyping was performed for eight SNPs covering the CYP2R1 gene in 2868 men with available samples of DNA. Subjects were followed up concerning incidence of fracture during five years.

Results: There was a significant genetic association with circulating levels of 25(OH)D (4.6-18.5% difference in mean values between SNP alleles), but there were no correlations with levels of calcium, phosphate, PTH or FGF23 for any genetic variant. No differences were found in fracture incidence between the variants. There was an inverse relationship between lower BMD and concomitant higher 25(OH)D for three of the haplotypes (p < 0.005).

Conclusions: Common variants in the CYP2R1 gene encoding Vitamin D 25-hydroxylase correlate with levels of circulating 25(OH)D but do not otherwise associate with measures of calcium and phosphate homeostasis. Presence of the specific haplotypes may be an indicator of risk for low 25(OH)D levels, and may in addition be correlated to bone mineral density.

sted, utgiver, år, opplag, sider
PUBLIC LIBRARY SCIENCE, 2018
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-373326 (URN)10.1371/journal.pone.0209268 (DOI)000454149400035 ()30576350 (PubMedID)
Forskningsfinansiär
Swedish Research Council, 2011-2535
Tilgjengelig fra: 2019-01-15 Laget: 2019-01-15 Sist oppdatert: 2019-01-15bibliografisk kontrollert
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