| 41. |
- Sandling, Johanna K., et al.
(författare)
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A candidate gene study of the type I interferon pathway implicates IKBKE and IL8 as risk loci for SLE
- 2011
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 19:4, s. 479-484
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Tidskriftsartikel (refereegranskat)abstract
- Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease in which the type I interferon pathway has a crucial role. We have previously shown that three genes in this pathway, IRF5, TYK2 and STAT4, are strongly associated with risk for SLE. Here, we investigated 78 genes involved in the type I interferon pathway to identify additional SLE susceptibility loci. First, we genotyped 896 single-nucleotide polymorphisms in these 78 genes and 14 other candidate genes in 482 Swedish SLE patients and 536 controls. Genes with P<0.01 in the initial screen were then followed up in 344 additional Swedish patients and 1299 controls. SNPs in the IKBKE, TANK, STAT1, IL8 and TRAF6 genes gave nominal signals of association with SLE in this extended Swedish cohort. To replicate these findings we extracted data from a genomewide association study on SLE performed in a US cohort. Combined analysis of the Swedish and US data, comprising a total of 2136 cases and 9694 controls, implicates IKBKE and IL8 as SLE susceptibility loci (P(meta)=0.00010 and P(meta)=0.00040, respectively). STAT1 was also associated with SLE in this cohort (P(meta)=3.3 × 10(-5)), but this association signal appears to be dependent of that previously reported for the neighbouring STAT4 gene. Our study suggests additional genes from the type I interferon system in SLE, and highlights genes in this pathway for further functional analysis.
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| 42. |
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| 43. |
- Shungin, Dmitry, et al.
(författare)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Tidskriftsartikel (refereegranskat)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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| 44. |
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| 45. |
- Simonsson, Bengt, et al.
(författare)
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Combination of pegylated IFN-alpha 2b with imatinib increases molecular response rates in patients with low- or intermediate-risk chronic myeloid leukemia
- 2011
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Ingår i: Blood. - Washington D.C. : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 118:12, s. 3228-3235
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Tidskriftsartikel (refereegranskat)abstract
- Biologic and clinical observations suggest that combining imatinib with IFN-alpha may improve treatment outcome in chronic myeloid leukemia (CML). We randomized newly diagnosed chronic-phase CML patients with a low or intermediate Sokal risk score and in imatinib-induced complete hematologic remission either to receive a combination of pegylated IFN-alpha 2b (Peg-IFN-alpha 2b) 50 mu g weekly and imatinib 400 mg daily (n = 56) or to receive imatinib 400 mg daily monotherapy (n = 56). The primary endpoint was the major molecular response (MMR) rate at 12 months after randomization. In both arms, 4 patients (7%) discontinued imatinib treatment (1 because of blastic transformation in imatinib arm). In addition, in the combination arm, 34 patients (61%) discontinued Peg-IFN-alpha 2b, most because of toxicity. The MMR rate at 12 months was significantly higher in the imatinib plus Peg-IFN-alpha 2b arm (82%) compared with the imatinib monotherapy arm (54%; intention-to-treat, P = .002). The MMR rate increased with the duration of Peg-IFN-alpha 2b treatment (andlt; 12-week MMR rate 67%, andgt; 12-week MMR rate 91%). Thus, the addition of even relatively short periods of Peg-IFN-alpha 2b to imatinib markedly increased the MMR rate at 12 months of therapy. Lower doses of Peg-IFN-alpha 2b may enhance tolerability while retaining efficacy and could be considered in future protocols with curative intent.
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| 46. |
- Sundström, Johan, Professor, 1971-, et al.
(författare)
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Risk factors for subarachnoid haemorrhage : a nationwide cohort of 950 000 adults
- 2019
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Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 48:6, s. 2018-2025
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Subarachnoid haemorrhage (SAH) is a devastating disease, with high mortality rate and substantial disability among survivors. Its causes are poorly understood. We aimed to investigate risk factors for SAH using a novel nationwide cohort consortium.METHODS: We obtained individual participant data of 949 683 persons (330 334 women) between 25 and 90 years old, with no history of SAH at baseline, from 21 population-based cohorts. Outcomes were obtained from the Swedish Patient and Causes of Death Registries.RESULTS: During 13 704 959 person-years of follow-up, 2659 cases of first-ever fatal or non-fatal SAH occurred, with an age-standardized incidence rate of 9.0 [95% confidence interval (CI) (7.4-10.6)/100 000 person-years] in men and 13.8 [(11.4-16.2)/100 000 person-years] in women. The incidence rate increased exponentially with higher age. In multivariable-adjusted Poisson models, marked sex interactions for current smoking and body mass index (BMI) were observed. Current smoking conferred a rate ratio (RR) of 2.24 (95% CI 1.95-2.57) in women and 1.62 (1.47-1.79) in men. One standard deviation higher BMI was associated with an RR of 0.86 (0.81-0.92) in women and 1.02 (0.96-1.08) in men. Higher blood pressure and lower education level were also associated with higher risk of SAH.CONCLUSIONS: The risk of SAH is 45% higher in women than in men, with substantial sex differences in risk factor strengths. In particular, a markedly stronger adverse effect of smoking in women may motivate targeted public health initiatives.
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| 47. |
- Torén, Kjell, 1952, et al.
(författare)
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The ratio FEV1/FVC and its association to respiratory symptoms-A Swedish general population study
- 2021
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Ingår i: Clinical Physiology and Functional Imaging. - : Wiley. - 1475-0961 .- 1475-097X. ; 41:2, s. 181-191
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Tidskriftsartikel (refereegranskat)abstract
- Chronic airflow limitation (CAL) can be defined as fixed ratio of forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) any respiratory symptom. In a cross-sectional general population study, 15,128 adults (50-64 years of age), 7,120 never-smokers and 8,008 ever-smokers completed a respiratory questionnaire and performed FEV1 and FVC after bronchodilation. We calculated different ratios of FEV1/FVC from 0.40 to 1.0 using 0.70 as reference category. We analysed odds ratios (OR) between different ratios and any respiratory symptom using adjusted multivariable logistic regression. Among all subjects, regardless of smoking habits, the lowest odds for any respiratory symptom was at FEV1/FVC = 0.82, OR 0.48 (95% CI 0.41-0.56). Among never-smokers, the lowest odds for any respiratory symptom was at FEV1/FVC = 0.81, OR 0.53 (95% CI 0.41-0.70). Among ever-smokers, the odds for any respiratory symptom was lowest at FEV1/FVC = 0.81, OR 0.43 (95% CI 0.16-1.19), although the rate of inclining in odds was small in the upper part, that is FEV1/FVC = 0.85 showed similar odds, OR 0.45 (95% CI 0.38-0.55). We concluded that the odds for any respiratory symptoms continuously decreased with higher FEV1/FVC ratios and reached a minimum around 0.80-0.85, with similar results among never-smokers. These results indicate that the optimal threshold associated with respiratory symptoms may be higher than 0.70 and this should be further investigated in prospective longitudinal studies.
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| 48. |
- Östgren, Carl Johan, et al.
(författare)
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Prevalence of atherosclerosis in individuals with prediabetes and diabetes compared to normoglycaemic individuals-a Swedish population-based study.
- 2023
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Ingår i: Cardiovascular diabetology. - : BioMed Central (BMC). - 1475-2840. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Patients with type 2 diabetes have an increased risk of death and cardiovascular events and people with diabetes or prediabetes have been found to have increased atherosclerotic burden in the coronary and carotid arteries. This study will estimate the cross-sectional prevalence of atherosclerosis in the coronary and carotid arteries in individuals with prediabetes and diabetes, compared with normoglycaemic individuals in a large population-based cohort.The 30,154 study participants, 50-64 years, were categorized according to their fasting glycaemic status or self-reported data as normoglycaemic, prediabetes, and previously undetected or known diabetes. Prevalence of affected coronary artery segments, severity of stenosis and coronary artery calcium score (CACS) were determined by coronary computed tomography angiography. Total atherosclerotic burden was assessed in the 11 clinically most relevant segments using the Segment Involvement Score and as the presence of any coronary atherosclerosis. The presence of atherosclerotic plaque in the carotid arteries was determined by ultrasound examination.Study participants with prediabetes (n = 4804, 16.0%) or diabetes (n = 2282, 7.6%) had greater coronary artery plaque burden, more coronary stenosis and higher CACS than normoglycaemic participants (all, p < 0.01). Among male participants with diabetes 35.3% had CACS ≥ 100 compared to 16.1% among normoglycaemic participants. For women, the corresponding figures were 8.9% vs 6.1%. The prevalence of atherosclerosis in the coronary arteries was higher in participants with previously undetected diabetes than prediabetes, but lower than in patients with known diabetes. The prevalence of any plaque in the carotid arteries was higher in participants with prediabetes or diabetes than in normoglycaemic participants.In this large population-based cohort of currently asymptomatic people, the atherosclerotic burden in the coronary and carotid arteries increased with increasing degree of dysglycaemia. The finding that the atherosclerotic burden in the coronary arteries in the undetected diabetes category was midway between the prediabetes category and patients with known diabetes may have implications for screening strategies and tailored prevention interventions for people with dysglycaemia in the future.
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| 49. |
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| 50. |
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